Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small cell lung cancer (ICTAN, GASTO1002): a randomized phase 3 trial

Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small cell lung cancer (ICTAN, GASTO1002): a randomized phase 3 trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small cell lung cancer (ICTAN, GASTO1002): a randomized phase 3 trial Si-Yu Wang, Ning Li, Wei Ou, Chao Cheng, Jian You, Lin Yang, Fengxia Chen, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4683245/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Jun, 2024 Read the published version in Journal of Clinical Oncology → Version 1 posted You are reading this latest preprint version Abstract The efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with completely resected EGFR-mutated non-small cell lung cancer (NSCLC) after adjuvant chemotherapy were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial, patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after platinum-based adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, to receive icotinib for 6 months or to undergo observation. The primary endpoint was DFS according to investigator assessment. This trial was terminated early. A total of 251 patients were randomized. Baseline characteristics were balanced among the groups. After a median follow-up of 61.4 months, 6 months of icotinib significantly improved DFS (hazard ratio (HR): 0.41, 95% confidence interval (CI), 0.27–0.62; P < 0.001) and overall survival (OS, HR: 0.56, 95% CI, 0.32–0.98; P = 0.041) compared with observation. Adjuvant icotinib of 12 months also significantly improved DFS (HR: 0.40, 95% CI, 0.27–0.61; P < 0.001) and OS (HR: 0.55, 95% CI, 0.32–0.96; P = 0.035) compared with observation. Adjuvant icotinib for 12 months did not improve DFS (HR: 0.97; P = 0.89) or OS (HR: 1.00; P = 0.99) compared with 6 months of this drug. Rates of adverse events of grade 3 or higher were 8.3%, 5.9% and 2.4% for the 12-month icotinib, 6-month icotinib and observation groups, respectively. The safety profile remained similar to that reported previously for icotinib. Adjuvant icotinib for 12 months and 6 months following adjuvant chemotherapy provided a significant DFS and OS benefit compared with observation in patients with completely resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile. Nevertheless, 12 months of icotinib had no additional benefit compared with 6 months. Health sciences/Diseases/Cancer/Lung cancer/Non-small-cell lung cancer Health sciences/Medical research/Clinical trial design/Randomized controlled trials icotinib EGFR mutation non-small cell lung cancer adjuvant chemotherapy. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer mortality worldwide 1 . Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers and most patients are diagnosed at a later stage 2 . Approximately 30% of patients with NSCLC present with resectable disease at the time of diagnosis 3 , 4 . For patients with resectable NSCLC, the standard-of-care treatment is surgery with curative intent, followed by adjuvant platinum-based chemotherapy for patients with stage II-IIIA and selected stage IB disease 5 . However, chemotherapy is associated with only a 5.4% absolute survival improvement at 5 years, and the risk of disease recurrence or death remains high for patients with resectable lung cancer 6 , 7 . Mutations of epidermal growth factor receptors (EGFR) occur more frequently in East-Asia patients (about 50%) than in Western patients (10%-15%) 8–10 . EGFR tyrosine kinase inhibitors (TKIs) have been established for patients with advanced NSCLC harboring EGFR mutations, with 3 generations of TKIs showing improvement in progression-free survival (PFS) compared with chemotherapy 2 . Based on the success in the advanced stage, EGFR-TKIs were assessed in the adjuvant setting. Two early studies (BR19 and RADIANT) investigating the value of EGFR-TKIs as adjuvant therapies did not select patients based on EGFR mutational status 11 , 12 . In both studies, no survival benefit was found after 2 years of a first-generation EGFR-TKI. In the single-arm SELECT study, encouraging disease-free survival (DFS) results were obtained after 2-year erlotinib for resectable EGFR-mutated NSCLC 13 . Moreover, in our phase II randomized trial evaluating gefitinib following chemotherapy as adjuvant therapy in patients with resected EGFR-mutated stage IIIA-N2 NSCLC, the addition of 6-month gefitinib significantly prolonged DFS compared with chemotherapy alone 14 . Icotinib is an EGFR-TKI of the first generation, which was approved in the second-line and first-line treatment for EGFR-mutated NSCLC based on the results from the ICOGEN and the CONVINCE trials, respectively 15 , 16 . The efficacy, safety and ideal treatment duration of adjuvant icotinib for patients with completely resected EGFR-mutated NSCLC were not known until 2014, when this study was initiated. This phase 3 ICTAN trial investigated whether icotinib following adjuvant chemotherapy improves clinical outcomes compared with observation in stage II-IIIA EGFR-mutated NSCLC. Results Patient characteristics From July 2014 through December 2021, 386 patients were screened for enrollment, and a total of 251 patients were randomly assigned, with 84 patients in the 12-month icotinib group, 84 patients in the 6-month icotinib group, and 83 patients in the observation group (Fig. 1 ). This trial was terminated early owing to slow accrual and the publication of EVIDENCE and ADAURA data. The baseline characteristics were generally well balanced between the groups: more than 60% of the patients were female, more than 85% were never smokers, and more than 59% had stage IIIA disease (Table 1 ). Almost all the patients had adenocarcinoma. For surgery, lobectomy was performed in the majority of the patients. Table 1 . Baseline characteristics of the intention-to-treat population. Icotinib of 12 months (n=84) Icotinib of 6 months (n=84) Observation (n=83) Age (years), median (minimum, maximum) 57 (34-75) 56 (33-75) 57 (24-75) Sex Male 30 (35.7) 29 (34.5) 30 (36.1) Female 54 (64.3) 55 (65.5) 53 (63.9) ECOG PS 0 41 (48.8) 43 (51.2) 38 (45.8) 1 40 (47.6) 39 (46.4) 42 (50.6) Missing 3 (3.6) 2 (2.4) 3 (3.6) Smoking status Never 72 (85.7) 73 (86.9) 72 (86.7) Former 5 (6.0) 6 (7.1) 5 (6.0) Current 7 (8.3) 5 (6.0) 6 (7.2) Histology Adenocarcinoma 83 (98.8) 83 (98.8) 83 (100.0) Other 1 (1.2) 1 (1.2) 0 Stage a IIA 6 (7.1%) 5 (6.0) 5 (6.0) IIB 28 (33.3) 29 (34.5) 29 (34.9) IIIA 50 (59.5) 50 (59.5) 49 (59.0) N stage N0 9 (10.7%) 8 (9.5%) 8 (9.6%) N1 30 (35.7%) 29 (34.5%) 29 (34.9%) N2 45 (53.6%) 47 (56.0%) 46 (55.4%) Surgery type Lobectomy 82 (97.6) 84 (100.0) 81 (97.6) Bilobectomy 1 (1.2) 0 1 (1.2) Pneumonectomy 1 (1.2) 1 (1.2) Side Left 39 (46.4) 36 (42.9) 40 (48.2) Right 45 (53.6) 48 (57.1) 43 (51.8) EGFR mutation Exon 19 deletion 46 (54.8) 47 (56.0) 44 (53.0) Exon 21 L858R 38 (45.2) 37 (44.0) 39 (47.0) Data are presented as n (%) unless stated otherwise. a Staging was determined according to the 7th edition of the AJCC TNM staging system for lung cancer. Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; AJCC, American Joint Committee on Cancer. For adjuvant chemotherapy, all four treatment cycles were completed in 68 (81.0%) patients in the 12-month icotinib group, 66 (78.6%) patients in the 6-month icotinib group, and 67 (80.7%) patients in the observation group. Three cycles of adjuvant chemotherapy were completed in 6, 7, and 7 patients in each group, respectively. In total, 70% of the patients received pemetrexed and carboplatin as adjuvant chemotherapy. A summary of the adjuvant chemotherapy cycles and regimens is provided in Table S1 . For treatment compliance, 65 patients (77.4%) in the 12-month icotinib group completed the planned 12-month treatment, and 66 patients (78.6%) in the 6-month icotinib group completed the planned 6-month treatment ( Table S2 ). In the 12-month icotinib group, 19 patients discontinued icotinib treatment because of patient decisions (n = 14), AEs (n = 4), or recurrence (n = 1). In the 6-month icotinib group, 18 patients discontinued icotinib treatment because of patient decisions (n = 15) and AEs (n = 3). The median duration of treatment was 12.1 months (interquartile range (IQR), 11.7–12.5) in the 12-month icotinib group and 6.5 months (IQR, 6.0–7.0) in the 6-month icotinib group. None of the patients in the icotinib groups were still receiving the study medication at the time of analysis. Efficacy The data cutoff date was January 15, 2024. The median duration of follow-up in the ITT population was 61.4 months (IQR, 44.9–79.8). The median follow-up for DFS was 64.5 months in the 12-month group, 60.5 months in the 6-month group, and 57.9 months in the observation group. By the time of the analysis, there had been 135 disease recurrence or death events. There were 40 (47.6%) disease relapse or death events in the 12-month group, 39 (46.4%) in the 6-month group, and 56 (67.5%) in the observation group. Adjuvant icotinib of 12 months significantly improved DFS (HR: 0.40, 95% CI, 0.27–0.61; P < 0.001) compared with observation (Fig. 2 ). Icotinib of 6 months also significantly improved DFS (HR: 0.41, 95% CI, 0.27–0.62; P < 0·001) compared with observation. Adjuvant icotinib of 12 months did not improve DFS (HR: 0.97; P = 0.89) compared with 6 months of this drug (Fig. 2 ). The median DFS was 61.8 months (95% CI, 43.3 to 80.3) for the 12-month icotinib group, 63.2 months (95% CI, 44.8 to 81.6) for the 6-month icotinib group compared with 23.7 months (95% CI, 16.5 to 30.9) for the observation group. The 5-year DFS for the 12-month icotinib, 6-month icotinib and observation groups were 51.3%, 50.1% and 24.8%, respectively (Fig. 2 ). The DFS benefit of 12-month icotinib over observation was generally consistent across most subgroups, including in the patients with either stage II or stage IIIA disease, those with either N0/N1 or N2 disease, and those who had exon 19 deletion or exon 21 L858R mutation (Fig. 3 a). In addition, the DFS benefit of 6-month icotinib over observation was also observed in most subgroups (Fig. 3 b). However, no differences in efficacy pertaining to icotinib duration were found in any of the subgroups ( Table S3 ). Among the patients with stage II disease, the 5-year DFS for the 12-month icotinib, 6-month icotinib and observation groups were 54.9% (95% CI, 38.9 to 74.9), 55.0% (95% CI, 33.9 to 77.9) and 29.3% (95% CI, 10.9 to 47.7); respectively ( Figure S1 a ). Among the patients with stage III disease, the 5-year DFS for the 12-month icotinib, 6-month icotinib and observation groups were 47.5% (95% CI, 32.4 to 62.6), 45.1% (95% CI, 30.6 to 59.6) and 21.9% (95% CI, 9.0 to 34.8); respectively ( Figure S1 b ). In the overall population, the lung was the most common first site of relapse, which occurred in 11 (13.1%), 12(14.3%), and 20 (24.1%) patients in the 12-month icotinib, 6-month icotinib, and observation groups, respectively ( Table S4 and Table S5 ). The brain was the second most common first site of relapse, which occurred in 10 (11.9%), 12(14.3%), and 15 (17.9%) in the 12-month icotinib, 6-month icotinib, and observation groups, respectively ( Table S4 and Table S5 ). The 12-month icotinib group had a significantly improved BMFS compared with the observation group, with a 5-year BMFS of 68.5% versus 54.5% (HR: 0.53, 95% CI, 0.32–0.88; P = 0.013; Figure S2 ). Icotinib of 6 months was also associated with an improved BMFS compared to observation, with the 5-year BMFS of 68.4% versus 54.5% (HR: 0.54, 95% CI, 0.33–0.90; P = 0.017; Figure S2 ). After disease relapse, 29, 29, and 44 patients in the 12-month, 6-month, and observation groups received a first subsequent therapy, respectively ( Table S6 ). Most patients received an EGFR-TKI-based treatment as their first subsequent therapy. Overall, 17 (42.5%) patients in the 12-month icotinib group, 12 (30.8%) patients in the 6-month icotinib group, and 9 (16.1%) patients in the observation group received a third-generation EGFR-TKI (osimertinib, aumolertinib, or furmonertinib) as the first subsequent therapy ( Table S6 ). By the time of the analysis, 73 death events had occurred, including 21 in the 12-month icotinib group, 20 in the 6-month icotinib group, and 32 in the observation group. OS was significantly more prolonged among the patients in the 12-month icotinib group than among those in the observation group (HR: 0.55, 95% CI, 0.32–0.96; P = 0.035; Fig. 4 ). OS was also significantly longer among those who had been assigned to the 6-month icotinib group than among those in the observation group (HR: 0.56, 95% CI, 0.32–0.98; P = 0.041; Fig. 4 ). However, adjuvant icotinib of 12 months did not improve OS compared with 6 months of this drug (HR: 1.00, 95% CI, 0.54–1.85; P = 0.99; Fig. 4 ). The 5-year OS for the 12-month, 6-month and observation groups were 74.5%, 74.0% and 65.1%, respectively. There were no significant differences between 12-month or 6-month icotinib and observation in the subgroups ( Figure S3 a and b ), possibly because the study was not powered to examine OS benefit within the subgroups. Safety A summary of the AEs is provided in Table S7 . AEs of any grade occurred in 65 (77.4%) patients in the 12-month group, 62 (73.8%) in the 6-month group, and 45 (54.2%) in the observation group. The most common AEs at any grade were rash (36.9%), diarrhea (21.4%), and raised aminotransferases (14.3%) in the 12-month group, and rash (38.1%), diarrhea (19.0%), and raised aminotransferases (13.1%) in the 6-month group, and leukopenia (8.4%), insomnia (8.4%), and raised aminotransferases (4.8%) in the observation group (Table 2 ). Table 2. Most common all-cause AEs reported in ≥5% of patients. 12-month icotinib 6-month icotinib Observation All-cause AEs Any grade Grade ≥ 3 Any grade Grade ≥ 3 Any grade Grade ≥ 3 Total a 65 (77.4%) 7 (8.3%) 62 (73.8%) 5 (5.9%) 45 (54.2%) 2 (2.4%) Rash 31 (36.9%) 3 (3.6%) 32 (38.1%) 2 (2.4%) 1 (1.2%) 0 Diarrhea 18 (21.4%) 1 (1.2%) 16 (19.0%) 1 (1.2%) 3 (3.6%) 0 Raised aminotransferases 12 (14.3%) 1 (1.2%) 11 (13.1%) 0 4 (4.8%) 0 Leukopenia 4 (4.8%) 1 (1.2%) 5 (6.0%) 0 7 (8.4%) 1 (1.2%) Insomnia 6 (7.1%) 1 (1.2%) 4 (4.8%) 1 (1.2%) 7 (8.4%) 0 Fatigue 5 (6.0%) 0 4 (4.8%) 1 (1.2%) 3 (3.6%) 1 (1.2%) Decreased appetite 4 (4.8%) 0 5 (6.0%) 0 2 (2.4%) 0 Oral ulcers 5 (6.0%) 0 3 (3.6%) 0 1 (1.2%) 0 Data are presented as n (%). All AEs were reported in at least 5% of the patients in either trial group, according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. a Total number of patients who had at least one AE; some patients had more than one AE. Abbreviations: AEs, adverse events. Grade 3 or worse AEs were reported for 7 (8.3%), 5 (5.9%), and 2 (2.4%) patients in the 12-month, 6-month, and observation groups, respectively. The grade 3 or worse AEs experienced in the 12-month group were rash in 3 patients (3.6%), diarrhea in 1 (1.2%), raised aminotransferases in 1 (1.2%), leukopenia in 1 (1.2%), and insomnia in 1 (1.2%). The grade 3 or worse AEs that occurred in the 6-month group were rash in 2 patients (2.4%), diarrhea in 1 (1.2%), insomnia in 1 (1.2%), and fatigue in 1 (1.2%). The grade 3 or worse AEs that occurred in the observation group were leukopenia in 1 patient (1.2%), and fatigue in 1 (1.2%). AEs leading to permanent treatment discontinuation were recorded in 4 (4.8%) and 3 (3.6%) patients in the 12-month and 6-month groups, respectively. No treatment-related deaths occurred in either group and no dose reductions were recorded. No new safety events have been observed since the previous reports for icotinib. Discussion This phase 3 open-label randomized ICTAN trial demonstrated a significant DFS benefit with 12-month or 6-month icotinib compared to observation in patients with completely resected EGFR-mutated stage II–IIIA NSCLC after adjuvant chemotherapy. The DFS benefit of 12- or 6-month icotinib over observation was generally consistent across most subgroups. The ICTAN trial also showed an improvement in OS and BMFS with icotinib versus observation in these patients. However, adjuvant icotinib of 12 months did not improve DFS, OS or BMFS compared with 6 months of this drug. The DFS noted among the patients treated with icotinib (median DFS, 61.8 months for the 12-month group and 63.2 months for the 6-month group) in the ICTAN trial was notably longer than that reported in the EVIDENCE trial (median DFS, 47.0 months) 17 . The results of this study also revealed an OS benefit of adjuvant icotinib in resected EGFR-mutated stage II–IIIA NSCLC. DFS benefit did not consistently translate into a significant difference in OS for first-generation EGFR-TKIs 17 – 19 . Compared with the EVIDENCE trial, reasons for the longer DFS and the OS benefit may largely relate to the study design of 100% adjuvant chemotherapy. Most randomized trials (including CTONG1104, EVIDENCE and IMPACT) evaluating adjuvant EGFR-TKIs were designed to compare an EGFR-TKI with standard chemotherapy, thus they did not include chemotherapy in the experimental group 17 , 20 – 22 . Although adjuvant chemotherapy was not addressed by the study design in ADAURA, the 5-year OS was higher among the stage II-IIIA patients with adjuvant chemotherapy than among those without chemotherapy in the osimertinib arm (87% vs. 80%) as well as in the placebo arm (75% vs. 66%) 23 , suggesting a potential survival benefit with adjuvant chemotherapy in this population. In vitro and clinical data suggest that chemotherapy combined with an EGFR-TKI may act in concert in EGFR-mutant NSCLC 24 , 25 . Thus, adjuvant chemotherapy, which is associated with a 16% reduction in the risk of recurrence or death in NSCLC, remains to be necessary for EGFR-mutated stage II-IIIA NSCLC when an EGFR-TKI was administered 26 , 27 . Researchers noted that the improvement in OS seen with osimertinib was not consistently observed with earlier generation EGFR-TKIs 17 – 19 , 23 , and this difference may owing to the ability to inhibit EGFR T790M and/or the superior intracranial activity of osimertinib. Although icotinib does not inhibit the T790M mutation, it is interesting to note that BMFS was improved with icotinib in the current trial. In the BRAIN trial, icotinib prolonged intracranial PFS compared with whole-brain irradiation plus chemotherapy (median intracranial PFS, 10.0 months vs. 4.8 months) 28 . Practically, early introduction of icotinib in the adjuvant setting could provide the opportunity for patients to receive the most effective first-line third-generation EGFR-TKI after recurrence. Indeed, more patients in the 12- or 6-month icotinib groups than in the observation group received a third-generation EGFR-TKI as their first subsequent therapy in the current study (42.5%, 30.8%, and 16.1%, respectively). These findings might partly explain the OS benefit of icotinib in this trial. In safety analyses, compared with the AEs reported in ADAURA, the AEs in the current study were lower; grade 3 or worse AEs were reported to be 23% in the osimertinib arm in ADAURA 23 , and 6–8% in the icotinib arms in our study. These results indicate that icotinib can be a treatment option to reduce the risk of brain metastases and improve survival in resected EGFR-mutated NSCLC. Adjuvant osimertinib for 3 years is considered a new standard for patients with resected EGFR-mutated NSCLC. However, whether 3, 2 or 1 year, or even half of a year is the optimal duration for adjuvant EGFR-TKIs remains to be determined. Thus, a key question is whether the survival benefit can be prolonged after discontinuation of the trial regimen. For first-generation EGFR-TKIs, drug resistance develops after 6–12 months of treatment, and more than 50% of the resistance is associated with the EGFR T790M mutation 29 , 30 . Moreover, after 1–2 years of osimertinib (targeting T790M mutation) treatment, new challenging resistance mechanisms eventually emerge 30 . In the CORIN trial, adjuvant icotinib of 1 year led to a significant increase of 3-year DFS compared with observation (96.1% vs. 84.0%) for stage IB NSCLC with EGFR mutations 31 . Compared with the stage IB subgroup in ADAURA, it seems that the CORIN trial achieved a similar clinical benefit with a first-generation EGFR-TKI and reduced treatment duration. With the results of the current study combined with those above, it should be highlighted that de-escalation of adjuvant TKI therapy might be feasible for resected EGFR-mutated NSCLC after adjuvant chemotherapy. Thus, efficacy, cost, toxicity, and treatment compliance should be taken into account in the selection of an EGFR-TKI and treatment duration in the adjuvant therapy of early-stage EGFR-mutated NSCLC. Circulating tumor DNA has shown its potential value in identifying patients who are at high risk of recurrence after resection 32 , 33 , and may facilitate individualized treatment in the adjuvant setting. The main limitation of our study was its early termination (due to slow accrual and the publication of EVIDENCE and ADAURA data), which led to a relatively small sample size and made the study to be underpowered for subgroup analysis in OS. Another limitation is that this study was delayed more than expected. During the course of this trial, several treatment practices changed for localized and advanced EGFR-mutated NSCLC. Other limitations include the non-blinded study design and 100% of the patients being of Asian ethnicity. Despite these limitations, our data provide crucial evidence on adjuvant a first-generation icotinib for patients with resected EGFR-mutated NSCLC after adjuvant chemotherapy. In conclusion, the findings of the ICTAN trial demonstrated that icotinib for 12 or 6 months prolonged DFS, OS and BMFS compared with observation for patients with completely resected stage II-IIIA EGFR-mutated NSCLC after adjuvant chemotherapy. Furthermore, icotinib was well tolerated, and no new safety issues were observed. These results support icotinib as a potential treatment option for these patients after adjuvant chemotherapy. Online Methods Study design and participants The ICTAN (GASTO1002) trial is a phase 3, randomized, open-label, multicenter trial conducted at 7 centers in China. Eligible patients were adult males or females (aged 18–70 years) with postsurgical pathological stage II-IIIA NSCLC (as classified according to the 7th edition of the American Joint Committee on Cancer (AJCC) TNM staging system 34 ); having completed at least two cycles of adjuvant platinum-based chemotherapy; having a confirmed EGFR mutation (exon 19 deletion and/or exon 21 L858R). Additional eligibility criteria were an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1, adequate hematological function, adequate liver and renal function, and a life expectancy of at least 1 year. Patients with a second primary malignancy in the past 5 years (except for cured basal cell carcinoma of the skin or cured in situ carcinoma of the uterine cervix); any prior systemic antitumor treatment other than adjuvant chemotherapy; previous radiotherapy; any unstable systemic disease (such as unstable heart disease or uncontrolled hypertension); or a history of interstitial lung disease were ineligible for this study. R0 resection of the lung cancer was mandatory (the definition of R0 is provided in the study protocol in the Supplementary Material). Additional eligibility criteria are provided in the study protocol (available in the Supplementary Material). This trial was conducted in accordance with the provisions of the Declaration of Helsinki, Good Clinical Practice guidelines and applicable laws and regulations. The protocol and any amendments were approved by the medical ethical committee of the Guangdong Association of Study of Thoracic Oncology (GASTO) and the independent ethics committee at each trial site. All participants provided written informed consent to participate. Randomization and blinding The randomization scheme was produced by the central staff of the GASTO via a computer-generated sequence with a minimization method. Randomization was stratified according to sex (male vs. female) and stage (II vs. IIIA). Eligible patients were randomized at a ratio of 1:1:1 to receive icotinib for 12 months, icotinib for 6 months or to undergo observation. All patients, investigators, and staffs involved in the study were unblinded to the treatment assignment. Procedures After completing chemotherapy, patients were randomized at a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, icotinib for 6 months or to undergo observation. The treatment continued until study completion, disease recurrence, intolerable toxicity, or death. Follow-up assessments were scheduled every 3 months for the first 2 years after randomization, every 6 months until 5 years, and every 12 months thereafter until disease relapse or death. The follow-up assessments comprised contrast-enhanced computed tomography (CT) of the chest and abdomen, brain magnetic resonance imaging (MRI), and bone scans. Brain MRI and bone scans were scheduled every 12 months or performed as indicated based on symptoms. Recurrence was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by the investigator. Post-recurrence therapy, which was chosen by investigators, was permitted. Safety assessments were performed from randomization to every visit. Adverse events (AEs) were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0. AEs were managed according to the AE management protocol. Quality of life (QoL) was assessed with the Functional Assessment of Cancer Therapy—Lung Cancer (FACT-L) questionnaire and the Lung Cancer Symptom Scale (LCSS). Endpoints The primary endpoint was DFS according to investigator assessment. DFS was defined as the duration from random assignment to disease recurrence or death, whichever occurs first. The secondary end points included overall survival (OS; defined as the time from random assignment to death from any cause), brain-metastasis-free survival (BMFS; defined as the time from randomization to brain metastasis or death, whichever comes first), safety, and QoL. QoL outcomes will be reported elsewhere. Statistical analysis On the basis of previous studies 6 , 11 , we assumed that the median DFS is 30 months for patients with EGFR-mutated stage II-IIIA NSCLC following adjuvant chemotherapy. We aimed to achieve 85% power at a two-sided α of 0.05 and an overall dropout rate of 5%. A total of 318 patients were needed to detect a 40% improvement in DFS with icotinib compared with chemotherapy for each comparison: 6 months of icotinib versus observation and 12 months of icotinib versus observation. This improvement corresponded to a hazard ratio (HR) of 0.6. A total of 198 DFS events were required for the final analysis. All analyses for efficacy were based on intention-to-treat (ITT) population, which included all randomized patients. Safety analyses were performed for all patients who received icotinib and those in the observation group. For efficacy comparisons, the Kaplan-Meier method was used to estimate time-to-event endpoints, with differences compared by log-rank tests with two-sided p values. A Cox proportional hazards model was used to estimate HRs, 95% confidence intervals (CIs), and Wald P value. A pre-planned subgroup analysis of DFS was performed for sex (male vs. female), stage (II vs. IIIA) and EGFR mutation type (exon 19 deletion vs. exon 21 L858R). The subgroup analysis of age (≥ 65 vs. <65), smoking history (ever vs. never), N stage (0 and 1 vs. 2), and side (left vs. right) was post hoc. This trial is registered with ClinicalTrials.gov, with the number NCT01996098. Declarations Acknowledgements This study was sponsored by Betta Pharmaceuticals Co., Ltd. The principal investigator Si-Yu Wang designed the study in collaboration with representatives of the study sponsor. The study sponsor provided funding and was involved in the study supervision, data collection, data interpretation, and writing and revising of this work. We express gratitude to the participants and their families. We also thank all investigators and their team members of the participating sites. We would like to thank Professor Qing Liu for his statistical assistance. This work was supported by the GuangDong Basic and Applied Basic Research Foundation (2024A1515030227, Ning Li). Author contributions S.-Y.W. and N.L. conceived and designed the research. N.L., W.O., C.C., J.Y., L.Y., F.-X.C., Y.L., Z.Y., B.-X.W., Z.-H.C., Y.-B.L., W.Y., F.X., G.D., X.-S.C., R.H., S.L., H.J., and X.-X.H. collected data. N.L., W.O., C.C., J.Y., H.L., and S.-Y.W. conducted data analysis. S.-Y.W. and the funder had the responsibility of study oversight. N.L., W.O., C.C., and S.-Y.W. contributed to the analysis of the data. All authors were involved in data interpretation. N.L., W.O., and S.-Y.W. wrote the first draft of the manuscript. All authors critically revised and approved the final version of the manuscript. Declaration of interests All authors declare no competing interests. Prior presentation Presented as an oral abstract at the 2024 ASCO Annual Meeting, Chicago, IL, May 31-June 4, 2024. Data sharing statement The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn). The datasets used and/or analyzed during the current study are available from the corresponding author on a reasonable request. References Bray, F. , et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74 , 229-263 (2024). Thai, A.A., Solomon, B.J., Sequist, L.V., Gainor, J.F. & Heist, R.S. Lung cancer. Lancet 398 , 535-554 (2021). Datta, D. & Lahiri, B. Preoperative evaluation of patients undergoing lung resection surgery. Chest 123 , 2096-2103 (2003). Molina, J.R., Yang, P., Cassivi, S.D., Schild, S.E. & Adjei, A.A. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 83 , 584-594 (2008). Kris, M.G. , et al. Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I to IIIA Completely Resected Non-Small-Cell Lung Cancers: American Society of Clinical Oncology/Cancer Care Ontario Clinical Practice Guideline Update. J Clin Oncol 35 , 2960-2974 (2017). Pignon, J.P. , et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 26 , 3552-3559 (2008). Goldstraw, P. , et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 11 , 39-51 (2016). Midha, A., Dearden, S. & McCormack, R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 5 , 2892-2911 (2015). Han, B. , et al. 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Adjuvant icotinib versus observation in patients with completely resected EGFR-mutated stage IB NSCLC (GASTO1003, CORIN): a randomised, open-label, phase 2 trial. EClinicalMedicine 57 , 101839 (2023). Li, N. , et al. Perioperative circulating tumor DNA as a potential prognostic marker for operable stage I to IIIA non-small cell lung cancer. Cancer 128 , 708-718 (2022). Pellini, B. & Chaudhuri, A.A. Circulating Tumor DNA Minimal Residual Disease Detection of Non-Small-Cell Lung Cancer Treated With Curative Intent. J Clin Oncol 40 , 567-575 (2022). Goldstraw, P. , et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2 , 706-714 (2007). Additional Declarations There is NO Competing Interest. Supplementary Files ICTANStatisticalAnalysisPlanV3.0.docx ICTANprotocolV3.0.docx Supplementarymaterial.docx Cite Share Download PDF Status: Published Journal Publication published 01 Jun, 2024 Read the published version in Journal of Clinical Oncology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4683245","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":329994503,"identity":"50dc0750-9a02-4791-9ee2-39dbc4de5df9","order_by":0,"name":"Si-Yu 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1","display":"","copyAsset":false,"role":"figure","size":543956,"visible":true,"origin":"","legend":"\u003cp\u003eTrial profile. All randomized patients were included in the ITT population for efficacy analyses. Safety analyses were performed for all patients who received icotinib and those in the observation group. ITT, intention-to-treat; N, number.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4683245/v1/d55210c867b3aa57e4246633.png"},{"id":60910710,"identity":"08762c0a-a22d-4d72-9c6c-2000606edbd9","added_by":"auto","created_at":"2024-07-23 12:52:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":487246,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier estimates of DFS by the investigator in the ITT population. DFS, disease-free survival; HR, hazard ratio; CI, confidence interval; ITT, intention-to-treat.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4683245/v1/7e8c61d8a2fdb967b23a0b1c.png"},{"id":60912020,"identity":"4d43b096-88c3-4941-894e-46fc2c58afb4","added_by":"auto","created_at":"2024-07-23 13:00:00","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":843034,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of DFS by subgroup, according to investigator assessment.\u003c/p\u003e\n\u003cp\u003e(a) Subgroup analyses of DFS for 12-month icotinib versus observation. (b) Subgroup analyses of DFS for 6-month icotinib versus observation. Subgroups were either pre-planned (sex, stage, and EGFR mutation type) or post hoc (age, smoking history, N stage, and side). DFS, disease-free survival; HR, hazard ratio; CI, confidence interval; EGFR, epidermal growth factor receptor.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4683245/v1/b729584a813172d48ed2775e.png"},{"id":60910714,"identity":"f5bd13b4-91cb-4ee7-bf66-c7fd2e8a0b2e","added_by":"auto","created_at":"2024-07-23 12:52:01","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":470471,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier estimates of OS in the ITT population. OS, overall survival; HR, hazard ratio; CI, confidence interval; ITT, intention-to-treat.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4683245/v1/5cef448de04b673f329471a4.png"},{"id":60913555,"identity":"de2096b9-4e5b-4acb-abf1-4edd608b3469","added_by":"auto","created_at":"2024-07-23 13:13:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3713156,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4683245/v1/cd92ff19-d13a-473b-a4ca-c81071bba59f.pdf"},{"id":60910707,"identity":"ef81f5c3-005a-4bf6-bac6-c8709645265e","added_by":"auto","created_at":"2024-07-23 12:52:00","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":74001,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"ICTANStatisticalAnalysisPlanV3.0.docx","url":"https://assets-eu.researchsquare.com/files/rs-4683245/v1/33ada53398b1164ac4188f84.docx"},{"id":60912021,"identity":"60c409b1-a08e-40ff-8c6a-b76e7b4c48bb","added_by":"auto","created_at":"2024-07-23 13:00:01","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":156167,"visible":true,"origin":"","legend":"","description":"","filename":"ICTANprotocolV3.0.docx","url":"https://assets-eu.researchsquare.com/files/rs-4683245/v1/4c64fe48016d0e3d2035aad3.docx"},{"id":60910712,"identity":"4693816e-7181-42eb-87cd-020def5712ea","added_by":"auto","created_at":"2024-07-23 12:52:00","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":778733,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-4683245/v1/978f6e659d974dff5d8aded0.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small cell lung cancer (ICTAN, GASTO1002): a randomized phase 3 trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLung cancer is the most frequently diagnosed cancer and the leading cause of cancer mortality worldwide\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers and most patients are diagnosed at a later stage\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Approximately 30% of patients with NSCLC present with resectable disease at the time of diagnosis\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. For patients with resectable NSCLC, the standard-of-care treatment is surgery with curative intent, followed by adjuvant platinum-based chemotherapy for patients with stage II-IIIA and selected stage IB disease\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. However, chemotherapy is associated with only a 5.4% absolute survival improvement at 5 years, and the risk of disease recurrence or death remains high for patients with resectable lung cancer\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMutations of epidermal growth factor receptors (EGFR) occur more frequently in East-Asia patients (about 50%) than in Western patients (10%-15%)\u003csup\u003e8\u0026ndash;10\u003c/sup\u003e. EGFR tyrosine kinase inhibitors (TKIs) have been established for patients with advanced NSCLC harboring EGFR mutations, with 3 generations of TKIs showing improvement in progression-free survival (PFS) compared with chemotherapy\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Based on the success in the advanced stage, EGFR-TKIs were assessed in the adjuvant setting. Two early studies (BR19 and RADIANT) investigating the value of EGFR-TKIs as adjuvant therapies did not select patients based on EGFR mutational status\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. In both studies, no survival benefit was found after 2 years of a first-generation EGFR-TKI. In the single-arm SELECT study, encouraging disease-free survival (DFS) results were obtained after 2-year erlotinib for resectable EGFR-mutated NSCLC\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Moreover, in our phase II randomized trial evaluating gefitinib following chemotherapy as adjuvant therapy in patients with resected EGFR-mutated stage IIIA-N2 NSCLC, the addition of 6-month gefitinib significantly prolonged DFS compared with chemotherapy alone\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIcotinib is an EGFR-TKI of the first generation, which was approved in the second-line and first-line treatment for EGFR-mutated NSCLC based on the results from the ICOGEN and the CONVINCE trials, respectively\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. The efficacy, safety and ideal treatment duration of adjuvant icotinib for patients with completely resected EGFR-mutated NSCLC were not known until 2014, when this study was initiated. This phase 3 ICTAN trial investigated whether icotinib following adjuvant chemotherapy improves clinical outcomes compared with observation in stage II-IIIA EGFR-mutated NSCLC.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient characteristics\u003c/h2\u003e\n \u003cp\u003eFrom July 2014 through December 2021, 386 patients were screened for enrollment, and a total of 251 patients were randomly assigned, with 84 patients in the 12-month icotinib group, 84 patients in the 6-month icotinib group, and 83 patients in the observation group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). This trial was terminated early owing to slow accrual and the publication of EVIDENCE and ADAURA data. The baseline characteristics were generally well balanced between the groups: more than 60% of the patients were female, more than 85% were never smokers, and more than 59% had stage IIIA disease (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Almost all the patients had adenocarcinoma. For surgery, lobectomy was performed in the majority of the patients.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Baseline characteristics\u0026nbsp;of the intention-to-treat population.\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"557\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003eIcotinib of 12 months (n=84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003eIcotinib of 6 months (n=84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003eObservation\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n=83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years), median (minimum, maximum)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e57 (34-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e56 (33-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e57 (24-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e30 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e29 (34.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e30 (36.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e54 (64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e55 (65.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e53 (63.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eECOG PS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e41 (48.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e43 (51.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e38 (45.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e40 (47.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e39 (46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e42 (50.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Missing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eSmoking status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Never\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e72 (85.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e73 (86.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e72 (86.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Former\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e6 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Current\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e6 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Adenocarcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e83 (98.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e83 (98.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e83 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eStage\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;IIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e6 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;IIB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e28 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e29 (34.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e29 (34.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;IIIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e50 (59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e50 (59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e49 (59.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eN stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;N0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e9 (10.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e8 (9.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e8 (9.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;N1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e30 (35.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e29 (34.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e29 (34.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;N2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e45 (53.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e47 (56.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e46 (55.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eSurgery type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Lobectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e82 (97.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e84 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e81 (97.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Bilobectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Pneumonectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eSide\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Left\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e39 (46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e36 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e40 (48.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Right\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e45 (53.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e48 (57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e43 (51.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eEGFR mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eExon 19 deletion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e46 (54.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e47 (56.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e44 (53.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.060931899641577%\" valign=\"top\"\u003e\n \u003cp\u003eExon 21 L858R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e38 (45.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.448028673835125%\" valign=\"top\"\u003e\n \u003cp\u003e37 (44.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.043010752688172%\" valign=\"top\"\u003e\n \u003cp\u003e39 (47.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eData are presented as n (%) unless stated otherwise.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003eStaging was determined according to the 7th edition of the AJCC TNM staging system for lung cancer.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAbbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; AJCC, American Joint Committee on Cancer.\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003eFor adjuvant chemotherapy, all four treatment cycles were completed in 68 (81.0%) patients in the 12-month icotinib group, 66 (78.6%) patients in the 6-month icotinib group, and 67 (80.7%) patients in the observation group. Three cycles of adjuvant chemotherapy were completed in 6, 7, and 7 patients in each group, respectively. In total, 70% of the patients received pemetrexed and carboplatin as adjuvant chemotherapy. A summary of the adjuvant chemotherapy cycles and regimens is provided in \u003cstrong\u003eTable \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/strong\u003e.\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003eFor treatment compliance, 65 patients (77.4%) in the 12-month icotinib group completed the planned 12-month treatment, and 66 patients (78.6%) in the 6-month icotinib group completed the planned 6-month treatment (\u003cstrong\u003eTable \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/strong\u003e). In the 12-month icotinib group, 19 patients discontinued icotinib treatment because of patient decisions (n\u0026thinsp;=\u0026thinsp;14), AEs (n\u0026thinsp;=\u0026thinsp;4), or recurrence (n\u0026thinsp;=\u0026thinsp;1). In the 6-month icotinib group, 18 patients discontinued icotinib treatment because of patient decisions (n\u0026thinsp;=\u0026thinsp;15) and AEs (n\u0026thinsp;=\u0026thinsp;3). The median duration of treatment was 12.1 months (interquartile range (IQR), 11.7\u0026ndash;12.5) in the 12-month icotinib group and 6.5 months (IQR, 6.0\u0026ndash;7.0) in the 6-month icotinib group. None of the patients in the icotinib groups were still receiving the study medication at the time of analysis.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eEfficacy\u003c/h2\u003e\n \u003cp\u003eThe data cutoff date was January 15, 2024. The median duration of follow-up in the ITT population was 61.4 months (IQR, 44.9\u0026ndash;79.8). The median follow-up for DFS was 64.5 months in the 12-month group, 60.5 months in the 6-month group, and 57.9 months in the observation group. By the time of the analysis, there had been 135 disease recurrence or death events. There were 40 (47.6%) disease relapse or death events in the 12-month group, 39 (46.4%) in the 6-month group, and 56 (67.5%) in the observation group. Adjuvant icotinib of 12 months significantly improved DFS (HR: 0.40, 95% CI, 0.27\u0026ndash;0.61; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared with observation (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Icotinib of 6 months also significantly improved DFS (HR: 0.41, 95% CI, 0.27\u0026ndash;0.62; P\u0026thinsp;\u0026lt;\u0026thinsp;0\u0026middot;001) compared with observation. Adjuvant icotinib of 12 months did not improve DFS (HR: 0.97; P\u0026thinsp;=\u0026thinsp;0.89) compared with 6 months of this drug (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The median DFS was 61.8 months (95% CI, 43.3 to 80.3) for the 12-month icotinib group, 63.2 months (95% CI, 44.8 to 81.6) for the 6-month icotinib group compared with 23.7 months (95% CI, 16.5 to 30.9) for the observation group. The 5-year DFS for the 12-month icotinib, 6-month icotinib and observation groups were 51.3%, 50.1% and 24.8%, respectively (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The DFS benefit of 12-month icotinib over observation was generally consistent across most subgroups, including in the patients with either stage II or stage IIIA disease, those with either N0/N1 or N2 disease, and those who had exon 19 deletion or exon 21 L858R mutation (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea). In addition, the DFS benefit of 6-month icotinib over observation was also observed in most subgroups (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb). However, no differences in efficacy pertaining to icotinib duration were found in any of the subgroups (\u003cstrong\u003eTable \u003cspan class=\"InternalRef\"\u003eS3\u003c/span\u003e\u003c/strong\u003e). Among the patients with stage II disease, the 5-year DFS for the 12-month icotinib, 6-month icotinib and observation groups were 54.9% (95% CI, 38.9 to 74.9), 55.0% (95% CI, 33.9 to 77.9) and 29.3% (95% CI, 10.9 to 47.7); respectively (\u003cstrong\u003eFigure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003ea\u003c/strong\u003e). Among the patients with stage III disease, the 5-year DFS for the 12-month icotinib, 6-month icotinib and observation groups were 47.5% (95% CI, 32.4 to 62.6), 45.1% (95% CI, 30.6 to 59.6) and 21.9% (95% CI, 9.0 to 34.8); respectively (\u003cstrong\u003eFigure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003eb\u003c/strong\u003e).\u003c/p\u003e\n \u003cp\u003eIn the overall population, the lung was the most common first site of relapse, which occurred in 11 (13.1%), 12(14.3%), and 20 (24.1%) patients in the 12-month icotinib, 6-month icotinib, and observation groups, respectively (\u003cstrong\u003eTable S4 and Table S5\u003c/strong\u003e). The brain was the second most common first site of relapse, which occurred in 10 (11.9%), 12(14.3%), and 15 (17.9%) in the 12-month icotinib, 6-month icotinib, and observation groups, respectively (\u003cstrong\u003eTable S4 and Table S5\u003c/strong\u003e). The 12-month icotinib group had a significantly improved BMFS compared with the observation group, with a 5-year BMFS of 68.5% versus 54.5% (HR: 0.53, 95% CI, 0.32\u0026ndash;0.88; P\u0026thinsp;=\u0026thinsp;0.013; \u003cstrong\u003eFigure \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/strong\u003e). Icotinib of 6 months was also associated with an improved BMFS compared to observation, with the 5-year BMFS of 68.4% versus 54.5% (HR: 0.54, 95% CI, 0.33\u0026ndash;0.90; P\u0026thinsp;=\u0026thinsp;0.017; \u003cstrong\u003eFigure \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/strong\u003e). After disease relapse, 29, 29, and 44 patients in the 12-month, 6-month, and observation groups received a first subsequent therapy, respectively (\u003cstrong\u003eTable S6\u003c/strong\u003e). Most patients received an EGFR-TKI-based treatment as their first subsequent therapy. Overall, 17 (42.5%) patients in the 12-month icotinib group, 12 (30.8%) patients in the 6-month icotinib group, and 9 (16.1%) patients in the observation group received a third-generation EGFR-TKI (osimertinib, aumolertinib, or furmonertinib) as the first subsequent therapy (\u003cstrong\u003eTable S6\u003c/strong\u003e).\u003c/p\u003e\n \u003cp\u003eBy the time of the analysis, 73 death events had occurred, including 21 in the 12-month icotinib group, 20 in the 6-month icotinib group, and 32 in the observation group. OS was significantly more prolonged among the patients in the 12-month icotinib group than among those in the observation group (HR: 0.55, 95% CI, 0.32\u0026ndash;0.96; P\u0026thinsp;=\u0026thinsp;0.035; Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). OS was also significantly longer among those who had been assigned to the 6-month icotinib group than among those in the observation group (HR: 0.56, 95% CI, 0.32\u0026ndash;0.98; P\u0026thinsp;=\u0026thinsp;0.041; Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). However, adjuvant icotinib of 12 months did not improve OS compared with 6 months of this drug (HR: 1.00, 95% CI, 0.54\u0026ndash;1.85; P\u0026thinsp;=\u0026thinsp;0.99; Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). The 5-year OS for the 12-month, 6-month and observation groups were 74.5%, 74.0% and 65.1%, respectively. There were no significant differences between 12-month or 6-month icotinib and observation in the subgroups (\u003cstrong\u003eFigure \u003cspan class=\"InternalRef\"\u003eS3\u003c/span\u003ea and b\u003c/strong\u003e), possibly because the study was not powered to examine OS benefit within the subgroups.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eSafety\u003c/h2\u003e\n \u003cp\u003eA summary of the AEs is provided in \u003cstrong\u003eTable S7\u003c/strong\u003e. AEs of any grade occurred in 65 (77.4%) patients in the 12-month group, 62 (73.8%) in the 6-month group, and 45 (54.2%) in the observation group. The most common AEs at any grade were rash (36.9%), diarrhea (21.4%), and raised aminotransferases (14.3%) in the 12-month group, and rash (38.1%), diarrhea (19.0%), and raised aminotransferases (13.1%) in the 6-month group, and leukopenia (8.4%), insomnia (8.4%), and raised aminotransferases (4.8%) in the observation group (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Most common all-cause AEs reported in \u0026ge;5% of patients.\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.61005199306759%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e12-month icotinib\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.61005199306759%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e6-month icotinib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.61005199306759%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eObservation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eAll-cause AEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003eAny grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003eGrade \u0026ge; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003eAny grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003eGrade \u0026ge; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003eAny grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003eGrade \u0026ge; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e65 (77.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e62 (73.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e5 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e45 (54.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eRash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e31 (36.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e32 (38.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eDiarrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e18 (21.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e16 (19.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eRaised aminotransferases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e12 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e11 (13.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e4 (4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eLeukopenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e4 (4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eInsomnia\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e6 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e4 (4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e4 (4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eDecreased appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e4 (4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.16984402079723%\" valign=\"top\"\u003e\n \u003cp\u003eOral ulcers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e3 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.17157712305026%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.43847487001733%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;Data are presented as n (%). All AEs were reported in at least 5% of the patients in either trial group, according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003eTotal number of patients who had at least one AE; some patients had more than one AE.\u003c/p\u003e\n \u003cp\u003eAbbreviations: AEs, adverse events.\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003eGrade 3 or worse AEs were reported for 7 (8.3%), 5 (5.9%), and 2 (2.4%) patients in the 12-month, 6-month, and observation groups, respectively. The grade 3 or worse AEs experienced in the 12-month group were rash in 3 patients (3.6%), diarrhea in 1 (1.2%), raised aminotransferases in 1 (1.2%), leukopenia in 1 (1.2%), and insomnia in 1 (1.2%). The grade 3 or worse AEs that occurred in the 6-month group were rash in 2 patients (2.4%), diarrhea in 1 (1.2%), insomnia in 1 (1.2%), and fatigue in 1 (1.2%). The grade 3 or worse AEs that occurred in the observation group were leukopenia in 1 patient (1.2%), and fatigue in 1 (1.2%). AEs leading to permanent treatment discontinuation were recorded in 4 (4.8%) and 3 (3.6%) patients in the 12-month and 6-month groups, respectively. No treatment-related deaths occurred in either group and no dose reductions were recorded. No new safety events have been observed since the previous reports for icotinib.\u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis phase 3 open-label randomized ICTAN trial demonstrated a significant DFS benefit with 12-month or 6-month icotinib compared to observation in patients with completely resected EGFR-mutated stage II\u0026ndash;IIIA NSCLC after adjuvant chemotherapy. The DFS benefit of 12- or 6-month icotinib over observation was generally consistent across most subgroups. The ICTAN trial also showed an improvement in OS and BMFS with icotinib versus observation in these patients. However, adjuvant icotinib of 12 months did not improve DFS, OS or BMFS compared with 6 months of this drug.\u003c/p\u003e \u003cp\u003eThe DFS noted among the patients treated with icotinib (median DFS, 61.8 months for the 12-month group and 63.2 months for the 6-month group) in the ICTAN trial was notably longer than that reported in the EVIDENCE trial (median DFS, 47.0 months)\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The results of this study also revealed an OS benefit of adjuvant icotinib in resected EGFR-mutated stage II\u0026ndash;IIIA NSCLC. DFS benefit did not consistently translate into a significant difference in OS for first-generation EGFR-TKIs\u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Compared with the EVIDENCE trial, reasons for the longer DFS and the OS benefit may largely relate to the study design of 100% adjuvant chemotherapy. Most randomized trials (including CTONG1104, EVIDENCE and IMPACT) evaluating adjuvant EGFR-TKIs were designed to compare an EGFR-TKI with standard chemotherapy, thus they did not include chemotherapy in the experimental group\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Although adjuvant chemotherapy was not addressed by the study design in ADAURA, the 5-year OS was higher among the stage II-IIIA patients with adjuvant chemotherapy than among those without chemotherapy in the osimertinib arm (87% vs. 80%) as well as in the placebo arm (75% vs. 66%)\u003csup\u003e23\u003c/sup\u003e, suggesting a potential survival benefit with adjuvant chemotherapy in this population. In vitro and clinical data suggest that chemotherapy combined with an EGFR-TKI may act in concert in EGFR-mutant NSCLC\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Thus, adjuvant chemotherapy, which is associated with a 16% reduction in the risk of recurrence or death in NSCLC, remains to be necessary for EGFR-mutated stage II-IIIA NSCLC when an EGFR-TKI was administered\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eResearchers noted that the improvement in OS seen with osimertinib was not consistently observed with earlier generation EGFR-TKIs\u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e, and this difference may owing to the ability to inhibit EGFR T790M and/or the superior intracranial activity of osimertinib. Although icotinib does not inhibit the T790M mutation, it is interesting to note that BMFS was improved with icotinib in the current trial. In the BRAIN trial, icotinib prolonged intracranial PFS compared with whole-brain irradiation plus chemotherapy (median intracranial PFS, 10.0 months vs. 4.8 months)\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Practically, early introduction of icotinib in the adjuvant setting could provide the opportunity for patients to receive the most effective first-line third-generation EGFR-TKI after recurrence. Indeed, more patients in the 12- or 6-month icotinib groups than in the observation group received a third-generation EGFR-TKI as their first subsequent therapy in the current study (42.5%, 30.8%, and 16.1%, respectively). These findings might partly explain the OS benefit of icotinib in this trial. In safety analyses, compared with the AEs reported in ADAURA, the AEs in the current study were lower; grade 3 or worse AEs were reported to be 23% in the osimertinib arm in ADAURA\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e, and 6\u0026ndash;8% in the icotinib arms in our study. These results indicate that icotinib can be a treatment option to reduce the risk of brain metastases and improve survival in resected EGFR-mutated NSCLC.\u003c/p\u003e \u003cp\u003eAdjuvant osimertinib for 3 years is considered a new standard for patients with resected EGFR-mutated NSCLC. However, whether 3, 2 or 1 year, or even half of a year is the optimal duration for adjuvant EGFR-TKIs remains to be determined. Thus, a key question is whether the survival benefit can be prolonged after discontinuation of the trial regimen. For first-generation EGFR-TKIs, drug resistance develops after 6\u0026ndash;12 months of treatment, and more than 50% of the resistance is associated with the EGFR T790M mutation\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Moreover, after 1\u0026ndash;2 years of osimertinib (targeting T790M mutation) treatment, new challenging resistance mechanisms eventually emerge\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. In the CORIN trial, adjuvant icotinib of 1 year led to a significant increase of 3-year DFS compared with observation (96.1% vs. 84.0%) for stage IB NSCLC with EGFR mutations\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Compared with the stage IB subgroup in ADAURA, it seems that the CORIN trial achieved a similar clinical benefit with a first-generation EGFR-TKI and reduced treatment duration. With the results of the current study combined with those above, it should be highlighted that de-escalation of adjuvant TKI therapy might be feasible for resected EGFR-mutated NSCLC after adjuvant chemotherapy. Thus, efficacy, cost, toxicity, and treatment compliance should be taken into account in the selection of an EGFR-TKI and treatment duration in the adjuvant therapy of early-stage EGFR-mutated NSCLC. Circulating tumor DNA has shown its potential value in identifying patients who are at high risk of recurrence after resection\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e, and may facilitate individualized treatment in the adjuvant setting.\u003c/p\u003e \u003cp\u003e The main limitation of our study was its early termination (due to slow accrual and the publication of EVIDENCE and ADAURA data), which led to a relatively small sample size and made the study to be underpowered for subgroup analysis in OS. Another limitation is that this study was delayed more than expected. During the course of this trial, several treatment practices changed for localized and advanced EGFR-mutated NSCLC. Other limitations include the non-blinded study design and 100% of the patients being of Asian ethnicity. Despite these limitations, our data provide crucial evidence on adjuvant a first-generation icotinib for patients with resected EGFR-mutated NSCLC after adjuvant chemotherapy.\u003c/p\u003e \u003cp\u003eIn conclusion, the findings of the ICTAN trial demonstrated that icotinib for 12 or 6 months prolonged DFS, OS and BMFS compared with observation for patients with completely resected stage II-IIIA EGFR-mutated NSCLC after adjuvant chemotherapy. Furthermore, icotinib was well tolerated, and no new safety issues were observed. These results support icotinib as a potential treatment option for these patients after adjuvant chemotherapy.\u003c/p\u003e"},{"header":"Online Methods","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThe ICTAN (GASTO1002) trial is a phase 3, randomized, open-label, multicenter trial conducted at 7 centers in China. Eligible patients were adult males or females (aged 18\u0026ndash;70 years) with postsurgical pathological stage II-IIIA NSCLC (as classified according to the 7th edition of the American Joint Committee on Cancer (AJCC) TNM staging system\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e); having completed at least two cycles of adjuvant platinum-based chemotherapy; having a confirmed EGFR mutation (exon 19 deletion and/or exon 21 L858R). Additional eligibility criteria were an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1, adequate hematological function, adequate liver and renal function, and a life expectancy of at least 1 year.\u003c/p\u003e \u003cp\u003ePatients with a second primary malignancy in the past 5 years (except for cured basal cell carcinoma of the skin or cured in situ carcinoma of the uterine cervix); any prior systemic antitumor treatment other than adjuvant chemotherapy; previous radiotherapy; any unstable systemic disease (such as unstable heart disease or uncontrolled hypertension); or a history of interstitial lung disease were ineligible for this study. R0 resection of the lung cancer was mandatory (the definition of R0 is provided in the study protocol in the Supplementary Material). Additional eligibility criteria are provided in the study protocol (available in the Supplementary Material).\u003c/p\u003e \u003cp\u003e This trial was conducted in accordance with the provisions of the Declaration of Helsinki, Good Clinical Practice guidelines and applicable laws and regulations. The protocol and any amendments were approved by the medical ethical committee of the Guangdong Association of Study of Thoracic Oncology (GASTO) and the independent ethics committee at each trial site. All participants provided written informed consent to participate.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eRandomization and blinding\u003c/h2\u003e \u003cp\u003eThe randomization scheme was produced by the central staff of the GASTO via a computer-generated sequence with a minimization method. Randomization was stratified according to sex (male vs. female) and stage (II vs. IIIA). Eligible patients were randomized at a ratio of 1:1:1 to receive icotinib for 12 months, icotinib for 6 months or to undergo observation. All patients, investigators, and staffs involved in the study were unblinded to the treatment assignment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eProcedures\u003c/h2\u003e \u003cp\u003eAfter completing chemotherapy, patients were randomized at a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, icotinib for 6 months or to undergo observation. The treatment continued until study completion, disease recurrence, intolerable toxicity, or death.\u003c/p\u003e \u003cp\u003eFollow-up assessments were scheduled every 3 months for the first 2 years after randomization, every 6 months until 5 years, and every 12 months thereafter until disease relapse or death. The follow-up assessments comprised contrast-enhanced computed tomography (CT) of the chest and abdomen, brain magnetic resonance imaging (MRI), and bone scans. Brain MRI and bone scans were scheduled every 12 months or performed as indicated based on symptoms. Recurrence was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by the investigator. Post-recurrence therapy, which was chosen by investigators, was permitted.\u003c/p\u003e \u003cp\u003eSafety assessments were performed from randomization to every visit. Adverse events (AEs) were graded according to the National Cancer Institute\u0026rsquo;s Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0. AEs were managed according to the AE management protocol. Quality of life (QoL) was assessed with the Functional Assessment of Cancer Therapy\u0026mdash;Lung Cancer (FACT-L) questionnaire and the Lung Cancer Symptom Scale (LCSS).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEndpoints\u003c/h2\u003e \u003cp\u003eThe primary endpoint was DFS according to investigator assessment. DFS was defined as the duration from random assignment to disease recurrence or death, whichever occurs first. The secondary end points included overall survival (OS; defined as the time from random assignment to death from any cause), brain-metastasis-free survival (BMFS; defined as the time from randomization to brain metastasis or death, whichever comes first), safety, and QoL. QoL outcomes will be reported elsewhere.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eOn the basis of previous studies\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, we assumed that the median DFS is 30 months for patients with EGFR-mutated stage II-IIIA NSCLC following adjuvant chemotherapy. We aimed to achieve 85% power at a two-sided α of 0.05 and an overall dropout rate of 5%. A total of 318 patients were needed to detect a 40% improvement in DFS with icotinib compared with chemotherapy for each comparison: 6 months of icotinib versus observation and 12 months of icotinib versus observation. This improvement corresponded to a hazard ratio (HR) of 0.6. A total of 198 DFS events were required for the final analysis.\u003c/p\u003e \u003cp\u003eAll analyses for efficacy were based on intention-to-treat (ITT) population, which included all randomized patients. Safety analyses were performed for all patients who received icotinib and those in the observation group. For efficacy comparisons, the Kaplan-Meier method was used to estimate time-to-event endpoints, with differences compared by log-rank tests with two-sided p values. A Cox proportional hazards model was used to estimate HRs, 95% confidence intervals (CIs), and Wald P value. A pre-planned subgroup analysis of DFS was performed for sex (male vs. female), stage (II vs. IIIA) and EGFR mutation type (exon 19 deletion vs. exon 21 L858R). The subgroup analysis of age (\u0026ge;\u0026thinsp;65 vs. \u0026lt;65), smoking history (ever vs. never), N stage (0 and 1 vs. 2), and side (left vs. right) was post hoc. This trial is registered with ClinicalTrials.gov, with the number NCT01996098.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;This study was sponsored by Betta Pharmaceuticals Co., Ltd.\u0026nbsp;The principal investigator Si-Yu Wang designed the study in collaboration with representatives of the study sponsor. The study sponsor provided funding and was involved in the study supervision, data collection, data interpretation, and writing and revising of this work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe express gratitude to the participants and their families. We also thank all investigators and their team members of the participating sites. We would like to thank Professor Qing Liu for his statistical assistance. This work was supported by the GuangDong Basic and Applied Basic Research Foundation (2024A1515030227, Ning Li).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;S.-Y.W. and N.L. conceived and designed the research. N.L., W.O., C.C., J.Y., L.Y., F.-X.C., Y.L., Z.Y., B.-X.W., Z.-H.C., Y.-B.L., W.Y., F.X., G.D., X.-S.C., R.H., S.L., H.J., and X.-X.H. collected data. N.L., W.O., C.C., J.Y., H.L., and S.-Y.W. conducted data analysis. S.-Y.W. and the funder had the responsibility of study oversight. N.L., W.O., C.C., and S.-Y.W. contributed to the analysis of the data. All authors were involved in data interpretation. N.L., W.O., and S.-Y.W. wrote the first draft of the manuscript. All authors critically revised and approved the final version of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrior presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePresented as an oral abstract at the 2024 ASCO Annual Meeting, Chicago, IL, May 31-June 4, 2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData sharing statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn). The datasets used and/or analyzed during the current study are available from the corresponding author on a reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray, F.\u003cem\u003e, et al.\u003c/em\u003e Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. \u003cem\u003eCA Cancer J Clin\u003c/em\u003e \u003cstrong\u003e74\u003c/strong\u003e, 229-263 (2024).\u003c/li\u003e\n\u003cli\u003eThai, A.A., Solomon, B.J., Sequist, L.V., Gainor, J.F. \u0026amp; Heist, R.S. Lung cancer. \u003cem\u003eLancet\u003c/em\u003e \u003cstrong\u003e398\u003c/strong\u003e, 535-554 (2021).\u003c/li\u003e\n\u003cli\u003eDatta, D. \u0026amp; Lahiri, B. 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Circulating Tumor DNA Minimal Residual Disease Detection of Non-Small-Cell Lung Cancer Treated With Curative Intent. \u003cem\u003eJ Clin Oncol\u003c/em\u003e \u003cstrong\u003e40\u003c/strong\u003e, 567-575 (2022).\u003c/li\u003e\n\u003cli\u003eGoldstraw, P.\u003cem\u003e, et al.\u003c/em\u003e The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. \u003cem\u003eJ Thorac Oncol\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, 706-714 (2007).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"icotinib, EGFR mutation, non-small cell lung cancer, adjuvant, chemotherapy. ","lastPublishedDoi":"10.21203/rs.3.rs-4683245/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4683245/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe efficacy, safety and ideal treatment duration of an adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with completely resected EGFR-mutated non-small cell lung cancer (NSCLC) after adjuvant chemotherapy were not known until 2014, when this study was initiated. In this phase 3 ICTAN trial, patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after platinum-based adjuvant chemotherapy were assigned in a 1:1:1 ratio to receive icotinib (125 mg, three times daily) for 12 months, to receive icotinib for 6 months or to undergo observation. The primary endpoint was DFS according to investigator assessment. This trial was terminated early. A total of 251 patients were randomized. Baseline characteristics were balanced among the groups. After a median follow-up of 61.4 months, 6 months of icotinib significantly improved DFS (hazard ratio (HR): 0.41, 95% confidence interval (CI), 0.27\u0026ndash;0.62; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and overall survival (OS, HR: 0.56, 95% CI, 0.32\u0026ndash;0.98; P\u0026thinsp;=\u0026thinsp;0.041) compared with observation. Adjuvant icotinib of 12 months also significantly improved DFS (HR: 0.40, 95% CI, 0.27\u0026ndash;0.61; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and OS (HR: 0.55, 95% CI, 0.32\u0026ndash;0.96; P\u0026thinsp;=\u0026thinsp;0.035) compared with observation. Adjuvant icotinib for 12 months did not improve DFS (HR: 0.97; P\u0026thinsp;=\u0026thinsp;0.89) or OS (HR: 1.00; P\u0026thinsp;=\u0026thinsp;0.99) compared with 6 months of this drug. Rates of adverse events of grade 3 or higher were 8.3%, 5.9% and 2.4% for the 12-month icotinib, 6-month icotinib and observation groups, respectively. The safety profile remained similar to that reported previously for icotinib. Adjuvant icotinib for 12 months and 6 months following adjuvant chemotherapy provided a significant DFS and OS benefit compared with observation in patients with completely resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile. Nevertheless, 12 months of icotinib had no additional benefit compared with 6 months.\u003c/p\u003e","manuscriptTitle":"Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small cell lung cancer (ICTAN, GASTO1002): a randomized phase 3 trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-23 12:51:55","doi":"10.21203/rs.3.rs-4683245/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fcf6fe80-aae7-4675-b294-e3420b7ffdc1","owner":[],"postedDate":"July 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":34928531,"name":"Health sciences/Diseases/Cancer/Lung cancer/Non-small-cell lung cancer"},{"id":34928532,"name":"Health sciences/Medical research/Clinical trial design/Randomized controlled trials"}],"tags":[],"updatedAt":"2024-07-23T13:12:56+00:00","versionOfRecord":{"articleIdentity":"rs-4683245","link":"https://doi.org/10.1200/JCO.2024.42.16_suppl.8004","journal":{"identity":"journal-of-clinical-oncology","isVorOnly":true,"title":"Journal of Clinical Oncology"},"publishedOn":"2024-06-01 13:12:56","publishedOnDateReadable":"June 1st, 2024"},"versionCreatedAt":"2024-07-23 12:51:55","video":"","vorDoi":"10.1200/JCO.2024.42.16_suppl.8004","vorDoiUrl":"https://doi.org/10.1200/JCO.2024.42.16_suppl.8004","workflowStages":[]},"version":"v1","identity":"rs-4683245","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4683245","identity":"rs-4683245","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}