Sustained Antiemetic Efficacy of Fosnetupitant versus Aprepitant in Carboplatin-based Chemotherapy: A Retrospective Observational Study

Sustained Antiemetic Efficacy of Fosnetupitant versus Aprepitant in Carboplatin-based Chemotherapy: A Retrospective Observational Study | 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 Research Article Sustained Antiemetic Efficacy of Fosnetupitant versus Aprepitant in Carboplatin-based Chemotherapy: A Retrospective Observational Study Hiroshi Inano, Yoshihito Morimoto, Atsushi Kawamura, Taichi Ikegami, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7701613/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Dec, 2025 Read the published version in International Journal of Clinical Oncology → Version 1 posted 5 You are reading this latest preprint version Abstract Background: Carboplatin (CBDCA) is highly emetogenic when administered at an area under the curve (AUC) ≥4, requiring triple antiemetic therapy, including an NK 1 receptor antagonist (NK 1 RA). Fosnetupitant (F-NTP), a long-acting NK 1 RA, may provide sustained receptor occupancy; however, its direct comparisons with aprepitant (APR) in CBDCA-based regimens between 0-168 h remain lacking. We aimed to evaluate the antiemetic efficacy of F-NTP versus APR between 1 week following chemotherapy. Methods: This retrospective single-center observational study included patients with cancer receiving CBDCA (AUC ≥4)-based regimens. Propensity score matching was performed using clinical factors. The primary endpoint was complete response (CR; no emesis or rescue medication) rate between 0–168 h. The secondary endpoints included phase-specific CR rates, time to treatment failure (TTF), and adverse events (AEs). Results: After matching, 242 patients were included in each group. The overall CR rate at 0–168 h was significantly higher with F-NTP (83.5%) than with APR (69.4%) ( p <0.001). F-NTP significantly prolonged TTF (hazard ratio =0.48, 95% confidence interval: 0.33–0.71, p <0.001). Multivariate analysis revealed female sex, younger age, and high CBDCA dose as significant risk factors for non-CR, while F-NTP use was a protective factor. AEs did not differ significantly between the groups and were mostly Grade 1. Conclusion: F-NTP demonstrated superior antiemetic efficacy to that of APR in CBDCA-based regimens, particularly maintaining higher CR rates through the acute and delayed phases. F-NTP was also well tolerated, supporting its potential as a strong prophylactic agent for preventing chemotherapy-induced nausea and vomiting. Fosnetupitant CINV NK1 RA CBDCA beyond-delayed Figures Figure 1 Figure 2 Figure 3 Introduction Carboplatin (CBDCA) is dosed according to the “Calvert formula,” where the dose is determined based on renal function and a target area under the concentration-time curve (AUC)[ 1 ]. This dosing strategy allows CBDCA to have a more favorable toxicity profile than that of cisplatin, with a lower risk of renal impairment. Consequently, CBDCA is safe and effective (even in older adult patients and those with comorbidities) and has a common application in cancer chemotherapy [ 1 ]. CBDCA is traditionally classified as a moderately emetogenic chemotherapy (MEC) agent; however, accumulating evidence from clinical trials has prompted its reclassification as a highly emetogenic chemotherapy when administered at an AUC of ≥ 4 [ 2 , 3 ]. Therefore, guideline-recommended prophylaxis currently includes triple antiemetic therapy, comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT₃RA), dexamethasone, and a neurokinin-1 receptor antagonist (NK 1 RA). A randomized controlled trial (RCT) of patients with gynecologic cancer demonstrated that the addition of aprepitant (APR) to a standard regimen significantly improved the complete response (CR; defined as no emesis or use of rescue antiemetics during the observation period) rate for vomiting [ 4 ]; however, another study reported no significant benefits of APR when combined with palonosetron [ 5 ]. A recent meta-analysis of 15 RCTs where approximately 60% of participants received CBDCA-containing MEC demonstrated that triple therapy significantly improved the CR and complete control rates compared with the effect of doublet therapy, supporting the utility of NK 1 RA addition in CBDCA-based regimens [ 6 ]. The use of intravenous fosaprepitant (F-APR), an NK 1 RA, has been limited in Japan. Retrospective observational studies have reported frequent vascular pain and phlebitis at the infusion site, prompting treatment modification to oral APR in approximately one quarter of patients [ 7 ] and limiting its adoption. Fosnetupitant (F-NTP), a long-acting NK 1 RA, was approved in Japan in 2022. F-NTP has demonstrated non-inferiority to F-APR concerning CR during the 0–120 h observation period after chemotherapy [ 8 ]. Moreover, it recently demonstrated higher control rates than did conventional NK 1 Ras, even in the newly defined beyond-delayed phase (120–168 h) introduced in the Japanese guidelines for appropriate antiemetic use [ 9 ]. However, there are limited comparative studies involving the specific evaluation of NK 1 RAs in CBDCA-based regimens between an extended 0–168-h observation period, including the beyond-delayed phase (Days 6–7). Therefore, we aimed to evaluate the antiemetic efficacy of NK 1 RAs between 1 week (0–168 h) following chemotherapy by directly comparing F-NTP with APR. Treatment effects were particularly focused on during the underexplored beyond-delayed phase to clarify the clinical significance of F-NTP in CBDCA-based regimens. Patients and Methods Study Population This single-center retrospective study included patients who received CBDCA-containing chemotherapy regimens at our institution between December 1, 2019, and March 31, 2024, and were administered an NK 1 RA as a prophylactic antiemetic therapy. The base-case population comprised patients who received intravenous F-NTP, and their responses and safety outcomes were compared with those of patients who received oral APR. Eligible patients had completed their first chemotherapy course, and all patients received triple antiemetic therapy containing a 5-HT₃ RA, dexamethasone, and an NK 1 RA. This study was approved by the Ethics Committee of Kitasato University Hospital (approval number: B24-048) and conducted in accordance with the Declaration of Helsinki. Informed consent was obtained through an opt-out procedure. Data Collection Data on sex, age, Eastern Cooperative Oncology Group performance status, cancer type, disease stage, recurrence status, actual CBDCA dose, concomitant anticancer drugs, concomitant radiotherapy, alcohol consumption history, smoking history, and the concomitant use of olanzapine were collected from the electronic medical records. Chemotherapy-induced nausea and vomiting (CINV), constipation, and hiccups were assessed as treatment-related adverse events (AEs). CINV was evaluated for up to 168 h after the first chemotherapy administration, and the following endpoints were analyzed: the proportion of patients achieving CR and time to treatment failure (TTF, defined as the time to the first emetic episode or the use of rescue antiemetics). The extended overall period (0–168 h) was further divided into acute (0–24 h), overall (0–120 h), extended-delayed (24–168 h), and beyond-delayed (120–168 h) phases. The AE severity was graded according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Endpoints The primary endpoint was the comparison of CR rates between the F-NTP and APR groups during the extended overall period (0–168 h). The secondary endpoints included the CR rates during the acute (0–24 h), overall (0–120 h), extended-delayed (24–168 h), and beyond-delayed (120–168 h) phases; the identification of risk factors for non-CR; TTF; and the incidence and severity of treatment-related AEs such as constipation and hiccups. Statistical Analysis To adjust for baseline differences between groups, propensity scores were calculated using five covariates: sex, age, alcohol consumption history, CBDCA dose, and the 5-HT₃ RA type that could influence the development of CINV. Subsequently, propensity score matching (1:1 nearest-neighbor method, caliper width = 0.2) was performed. Baseline characteristics were compared using Fisher’s exact test for categorical variables, Mann–Whitney U test for age, and Student’s t-test for CBDCA dose. In addition, Fisher’s exact test was used to compare the CR rates between the groups. To identify the factors associated with non-CR, univariate and multivariate logistic regression analyses were conducted using five covariates (sex, age, alcohol consumption, CBDCA dose, and F-NTP administration), and the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. TTF was analyzed using the Kaplan–Meier method, and group differences were assessed using the log-rank test. All statistical analyses were performed using SPSS version 29 (IBM Corp., Armonk, NY, USA), and a p- value < 0.05 was considered statistically significant. Results Patient Characteristics Of the 856 patients who received CBDCA-based chemotherapy regimens, 10 were excluded owing to inappropriate antiemetic administration. In addition, we excluded 18 participants owing to missing evaluation data, leaving 828 patients eligible for the analysis (Fig. 1 ). Based on the prophylactic antiemetic regimen administered, 272 and 556 patients were assigned to the F-NTP and APR groups, respectively. Following propensity score matching, 242 patients were included in each group. The distributions of the propensity scores for the five matched factors before and after matching are summarized in Table 1 . The other baseline characteristics are presented in Table 2 . Variables such as sex, age, alcohol consumption history, CBDCA dose, and the 5-HT₃ RA type were well balanced between groups. Table 1 Patient characteristics Before propensity score matching After propensity score matching APR group F-NTP group APR group F-NTP group Characteristics (N = 556) (N = 272) p -value (N = 242) (N = 242) p -value Sex n (%) < 0.001 0.856 Male 180 (32.4) 161 (59.2) 133 (55.0) 136 (56.2) Female 376 (67.6) 111 (40.8) 109 (45.0) 106 (43.8) Age, years (median, range) 66 (28–91) 73 (35–89) < 0.001 71 (28–86) 72 (35–88) 0.394 Alcohol habit, n (%) 216 (38.8) 150 (55.1) < 0.001 130 (53.7) 133 (55.0) 0.855 CBDCA dose AUC, Average (SD) 5.39 (0.79) 5.21 (0.70) 0.001 5.10 (0.93) 5.21 (0.71) 0.132 5-HT 3 RA, n (%) 0.926 Palonosetron 146 (26.3) 177 (65.1) < 0.001 146 (60.3) 148 (61.2) Granisetron 410 (73.7) 95 (34.9) 96 (39.7) 94 (38.8) F-NTP, fosnetupitant; APR, aprepitant; CBDCA, carboplatin; AUC, Area Under the Curve; 5-HT 3 RA, 5-hydroxytryptamine-3 receptor antagonist Table 2 Other patient characteristics APR group (N = 242) F-NTP group (N = 242) ECOG performance status, n (%) 0 134 (55.4) 150 (62.0) 1 96 (39.7) 63 (26.0) 2 10 (4.1) 17 (7.0) 3 2 (0.8) 11 (4.5) 4 0 (0) 1 (0.4) Tumor type, N (%) Lung cancer 137 (56.6) 160 (66.1) Gynecological cancer 48 (19.8) 37 (15.3) Urothelial carcinoma 26 (10.7) 22 (9.1) Breast cancer 8 (3.3) 2 (0.8) Others 23 (9.5) 21 (8.7) Cancer stage, N (%) I 17 (7.0) 8 (3.3) II 17 (7.0) 8 (3.3) III 37 (15.3) 47 (19.4) IV 117 (48.3) 133 (55.0) Recurrence 54 (22.3) 46 (19.0) Concomitant anticancer drugs, N (%) 240 (99.2) 231 (95.5) Moderate risk 0 (0) 2 (0.8) Combined with radiation, N (%) 3 (1.2) 12 (5.0) Smoking history, N (%) 143 (59.1) 162 (66.9) Prophylactic administration of olanzapine, N (%) 5 (2.1) 4 (1.7) Dose of dexamethasone Day 1 Intravenous 0 0 (0) 1 (0.4) 3.3 1 (0.4) 68 (28.1) 4.95 1 (0.4) 0 (0) 6.6 56 (23.1) 44 (18.2) 9.9 121 (50.0) 91 (37.6) 13.2 2 (0.8) 0 (0) 16.5 55 (22.7) 38 (15.7) 33.0 6 (2.5) 0 (0) Day 2 and after Oral administration 61 (25.2) 52 (21.5) Intravenous 26 (10.7) 57 (23.6) F-NTP, fosnetupitant; APR, aprepitant; ECOG, Eastern Cooperative Oncology Group CR Rate for Each Group The CR rates during the extended overall period (0–168 h) are shown in Fig. 2 . The CR rate during this period was significantly higher in the F-NTP group than in the APR group (83.5% vs. 69.4%; p < 0.001). Table 3 summarizes the patient populations that achieved CR at each time point. F-NTP achieved significantly higher CR rates than did APR during the acute (0–24 h; 99.6% vs. 94.2%; p < 0.001), overall (0–120 h; 88.4% vs. 74.4%; p < 0.001), and extended delayed (24–168 h; 83.5% vs. 69.4%; p < 0.001) phases. In contrast, the CR rates during the beyond-delayed phase (120–168 h) were significantly higher in the APR group than in the F-NTP group (93.8% vs. 86.4%; p = 0.009). Table 3 Comparison of CR rates between APR and F-NTP APR group (N = 242) F-NTP group (N = 242) p -value Acute (0–24 h) 94.2 99.6 < 0.001 Overall (0–120 h) 74.4 88.4 < 0.001 Extended-delayed (24–168 h) 69.4 83.5 < 0.001 Beyond-delayed (120–168 h) 93.8 86.4 0.009 CR, complete response; F-NTP, fosnetupitant; APR, aprepitant Examination of Risk Factors In real-world practice, the effect of patient characteristics on CINV control and anticancer efficacy is partially understood. Therefore, we evaluated the effect of F-NTP on CR while adjusting for clinically significant confounders. The univariate and multivariate analyses of the risk factors for non-CR during the extended overall period (0–168 h) are presented in Table 4 . Table 4 Comparison of CR rates between APR and F-NTP Univariate analysis Multivariate analysis Factor OR 95% CI p -value OR 95% CI p -value Female sex 2.47 1.60–3.80 < 0.001 2.18 1.35–3.51 0.001 Age 0.96 0.95–0.98 < 0.001 0.97 0.95–0.99 0.009 Alcohol habit, n (%) 0.83 0.55–1.27 0.396 0.98 0.62–1.56 0.936 CBDCA dose (AUC) 1.49 1.10–2.02 0.001 1.47 1.11–1.94 0.008 F-NTP 0.45 0.29–0.70 < 0.001 0.42 0.27–0.66 < 0.001 CR, complete response; F-NTP, fosnetupitant; APR, aprepitant; CBDCA, carboplatin; AUC, Area Under the Curve In the univariate analysis, female sex, younger age, and high CBDCA dose were significantly associated with non-CR, whereas F-NTP administration was associated with a reduced non-CR risk. However, alcohol consumption showed no significant association. In the multivariate analysis including all candidate risk factors, female sex increased the non-CR risk by approximately two-fold (OR, 2.18; p = 0.001). Age was protective, with each additional year reducing the non-CR risk by approximately 3% (OR, 0.97; p = 0.009). A high CBDCA dose increased the risk, with an OR of 1.47 per 1-unit increase in the AUC ( p = 0.008). The use of F-NTP was identified as an independent factor that significantly reduced non-CR risk compared with the APR effect (OR, 0.42; p < 0.001). Similar to the event in the univariate analysis, alcohol consumption showed no significant association in the multivariate analysis. TTF The Kaplan–Meier curves are shown in Fig. 3 . The log-rank test revealed that TTF was significantly longer in the F-NTP group than in the APR group ( p < 0.001). At 168 h, the median TTF was not reached in the F-NTP group, whereas it was reached at 120 h in the APR group. Notably, the curves diverged early in the delayed phase (24–120 h), suggesting a lower incidence of CINV in the F-NTP group. The Cox proportional hazards model demonstrated that F-NTP reduced the risk of treatment failure by approximately 52% compared with the effect of APR (hazard ratio [HR]: 0.48; 95% CI: 0.33–0.71). AEs The incidence of AEs is summarized in Table 5 . Constipation occurred in 59.5% of the F-NTP group participants and in 57.9% of those in the APR group, implying no significant differences ( p = 0.712). Most cases were Grade 1 or 2, and only one case of Grade 3 constipation (0.4%) was observed in the F-NTP group. Table 5 Comparison of the incidence of adverse events between the F-NTP and F-APR groups APR group (N = 242) F-NTP group (N = 242) p -value Constipation 140 (57.9) 144 (59.5) 0.782 Grade 1 116 (47.9) 122 (50.4) Grade 2 24 (9.9) 21 (8.7) Grade 3 0 (0) 1 (0.4) Hiccup 30 (12.4) 18 (7.4) 0.094 Grade 1 23 (9.5) 10 (4.1) Grade 2 7 (2.9) 7 (2.9) Grade 3 0 (0) 1 (0.4) F-NTP, fosnetupitant; APR, aprepitant Hiccups occurred in 7.4% of the participants in the F-NTP group and in 12.4% of those in the APR group, showing a lower trend with F-NTP treatment but without statistical significance ( p = 0.094). Most hiccup events were Grade 1 or 2; only one Grade 3 hiccup event (0.4%) occurred in the F-NTP group. Discussion This is the first study on the direct comparison of F-NTP and APR potentials to prevent CINV between 1 week (0–168 h) following CBDCA-based chemotherapy. Evident imbalances in baseline characteristics existed between the two groups; thus, we applied propensity score matching to minimize confounding factors. The CR rate during the extended overall period (0–168 h) was significantly higher in the F-NTP group than in the APR group. Notably, the curves for treatment success began to diverge early in the delayed phase (24–120 h), highlighting the sustained antiemetic efficacy of F-NTP. Although the CR rate of the APR group slightly exceeded that of the F-NTP group in the beyond-delayed phase (120–168 h), the F-NTP group demonstrated superior long-term efficacy. Furthermore, in the multivariate analysis, F-NTP therapy emerged as an independent predictor of a reduced non-CR risk (OR, 0.42). In addition, TTF analysis revealed that the risk of treatment failure was reduced by approximately 53% in the F-NTP group compared with that in the APR group (HR, 0.47), and this effect persisted up to 168 h. These findings support the long-term efficacy of F-NTP in patients receiving CBDCA-based regimens. During the extended overall phase (0–168 h), the F-NTP group achieved a CR rate of 83.5%, compared with 69.4% in the APR group. These results are consistent with the findings of previous studies on patients receiving cisplatin (CDDP)-based regimens [ 9 ], and may be partly explained by the pharmacokinetic properties of F-NTP. The terminal half-life of the active metabolite of APR in healthy volunteers was 13.9 ± 4.8 h [ 10 ], whereas that of F-NTP was markedly longer (70.4 ± 22.3 h) [ 11 ]. Moreover, in real-world settings, where patients are older than those enrolled in clinical trials, adherence concerns with orally administered drugs such as APR may further contribute to the differences in efficacy between APR and intravenous regimens pre-integrated with F-NTP or fosaprepitant (F-APR) [ 12 ] During the beyond-delayed phase (120–168 h), APR achieved a higher CR rate (93.8%) than did F-NTP (86.4%). There are several possible explanations for the discrepancy. Patients who required rescue medication during the delayed phase (24–120 h) were more in the APR group than in the F-NTP group, which may have subsequently suppressed CINV during the beyond-delayed phase. Conversely, because patients in the F-NTP group achieved favorable control in the extended overall period, the use of rescue medication was limited, possibly resulting in a decline in antiemetic protection in the beyond-delayed phase. Additionally, the relatively large sample size in this study may have facilitated the detection of statistically significant differences, even when the actual clinical differences between the groups were small. Beyond these considerations, the temporal pattern of efficacy observed in our study differs from those in previous reports on CDDP-based regimens. CDDP shows a slower increase and a more sustained plasma concentration of free platinum, prolonging emetogenic stimulation and usually leading to larger differences in the beyond-delayed phase [ 9 ]. In contrast, CBDCA exhibits a rapid increase and earlier disappearance, resulting in a higher emetogenic risk during the acute and early delayed phases, but a diminished impact in the beyond-delayed phase [ 13 ]. Consequently, group differences in CBDCA were most evident in the early period, whereas in the beyond-delayed phase, patient-related factors may have played a more dominant role in determining the outcomes. To explore the risk factors for CINV, we analyzed five variables (sex, age, alcohol intake, CBDCA dose, and F-NTP use) using univariate and multivariate models based on previous reports [ 14 , 15 ]. Female sex, younger age, and a high CBDCA dose were confirmed as significant risk factors for non-CR, consistent with previous reports. In contrast, alcohol consumption was not a significant factor, possibly because the retrospective design precluded the accurate quantification of drinking habits from clinical records. Notably, F-NTP use emerged as an independent predictor of a reduced non-CR risk. Kaplan–Meier curves revealed that the F-NTP group differed early from the APR group, maintaining higher event-free rates for 168 h. This visual and statistical concordance indicates that F-NTP prolonged treatment success. The difference was particularly pronounced between 24 and 120 h, which appeared to be the primary driver of the overall difference. Two factors could explain this observation. The first condition is the pharmacological characteristics of CBDCA. The rapid increase of CBDCA in free platinum concentration provides strong emetogenic stimulation from the acute phase onward [ 16 ]. In contrast to the reports on CDDP-based regimens [ 9 ], where differences usually emerge later in the delayed phase, effective early control during the acute and early delayed phases appears critical in CBDCA regimens, and F-NTP may provide this advantage. The second factor is the receptor occupancy profile of F-NTP. Following intravenous administration, F-NTP undergoes rapid conversion to its active metabolite, achieving high NK₁ receptor occupancy promptly and sustaining it over time [ 17 ]. In contrast, APR, administered orally, is subject to absorption and distribution delays, and its receptor occupancy gradually declines [ 18 ]. Thus, in addition to “duration,” the “rapidity” of NK₁ receptor blockade by F-NTP may align more closely with the early emetogenic challenge of CBDCA, accounting for its superiority in the acute to early delayed phases. NK₁ RAs have been traditionally emphasized for their persistence; however, our findings suggest that onset and potency constitute key determinants of CINV control. Regarding AEs, the typical side effects of NK₁RAs include hiccups and constipation, which, if severe, may trigger nausea and vomiting. Therefore, careful monitoring is necessary. In this study, the incidence of AEs showed no significant differences between the F-NTP and APR groups. Moreover, most events were Grade 1 in both groups, and no critical AEs were reported, indicating the favorable tolerability of both agents. This study has some limitations. First, it relied on retrospectively collected data from a single center, and the residual bias from patient background may not have been fully eliminated; thus, we applied propensity score matching to account for major confounders. Second, information on certain risk factors previously reported for CINV, such as a history of hyperemesis gravidarum or motion sickness, was unavailable in our dataset, which may have influenced our results. F-NTP demonstrated superior CINV control compared with that of APR during an extended overall period (0–168 h) in patients receiving CBDCA-based chemotherapy. F-NTP was associated with a significant reduction in nausea and vomiting without causing severe AEs and was well tolerated. These findings support the clinical utility of F-NTP in CBDCA-based regimens. Declarations Conflict of Interest: The authors declare no competing interests. Funding : This study received no funding. Data Availability : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics Approval: This study was approved by the Ethics Committee of Kitasato University Hospital (approval number: B24-048) and conducted in accordance with the Declaration of Helsinki. Informed consent was obtained through an opt-out procedure. Author contributions : Conceptualization: Hiroshi Inano; Data curation: Hiroshi Inano; Formal Analysis: Yoshihito Morimoto; Funding acquisition: Hiroshi Inano; Investigation: Atsushi Kawamura, Taichi Ikegami, Tomoki Niizuma, Kanata Kitagawa, Rie Usami, Kozue Nakagomi, Yuri Anzo, Misaki Uchikawa; Methodology: Hiroshi Inano; Project administration: Hiroshi Inano; Resources: Hiroshi Inano; Software: Hiroshi Inano; Supervision: Katsuya Otori; Validation: Hiroshi Inano; Visualization: Yoshihito Morimoto; Writing – original draft: Hiroshi Inano; Writing – review & editing: Yoshihito Morimoto, Haruki Yamamoto, Aiko Shono, Kazuhiro Watanabe. All authors read and approved the final manuscript. Acknowledgments: Not applicable. References Schwenk MH (2024) Carboplatin Dosing on the Basis of Renal Function: 30+ Years after Calvert. 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J Clin Pharmacol 47:834-840. https://doi.org/10.1177/0091270007301800 Cite Share Download PDF Status: Published Journal Publication published 09 Dec, 2025 Read the published version in International Journal of Clinical Oncology → Version 1 posted Editorial decision: Major revisions 28 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers invited by journal 13 Oct, 2025 Editor assigned by journal 26 Sep, 2025 First submitted to journal 24 Sep, 2025 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. 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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-7701613","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":529092983,"identity":"f2c1321b-20df-4f88-ae31-d7d5891189d7","order_by":0,"name":"Hiroshi Inano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYBACNghlY8CGKs5DUEuaARuYlUCEFig4bMCAqgUP4GPgPfi5oOK8MZ988+MPP3/YMBgcYH74gUHmDh6H8SVLzzhz24yNjc1MsichDaiFzViCgecZbi3ybwykedtu2wD9YsbAk3C4fsMBIIOB5zAeW3iMf/O2nQNqYf/88U/CYaAt7N8IaTED2nIA6DAeA2kesBYegraYWfOcSTZmY8spk5ZJS2OQPMxTLJGAxy/yDTzGt3kq7AznNx/f/PGNjQ0D3/H2jR8+9uAOMSyAGYgTew6QogUMfpCuZRSMglEwCoYtAAAyBkOfEtXSCgAAAABJRU5ErkJggg==","orcid":"","institution":"Kitasato University Hospital: Kitasato Daigaku Byoin","correspondingAuthor":true,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Inano","suffix":""},{"id":529092984,"identity":"5039bf29-fa4c-495c-81e9-9c597eaf9e3a","order_by":1,"name":"Yoshihito Morimoto","email":"","orcid":"","institution":"Showa Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Yoshihito","middleName":"","lastName":"Morimoto","suffix":""},{"id":529092985,"identity":"e9772a68-cbd1-44d4-bae9-233bd70a2b10","order_by":2,"name":"Atsushi Kawamura","email":"","orcid":"","institution":"Kitasato University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Atsushi","middleName":"","lastName":"Kawamura","suffix":""},{"id":529092986,"identity":"a06fa067-6df8-4032-97fe-bf3451bb7169","order_by":3,"name":"Taichi Ikegami","email":"","orcid":"","institution":"Kitasato University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Taichi","middleName":"","lastName":"Ikegami","suffix":""},{"id":529092987,"identity":"cd022f04-4aba-4116-b85f-dd9110569231","order_by":4,"name":"Tomoki Niizuma","email":"","orcid":"","institution":"Kitasato University 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kozue","middleName":"","lastName":"Nakagomi","suffix":""},{"id":529092991,"identity":"a931c200-2216-40ab-b2b0-a99ad2590d1a","order_by":8,"name":"Yuri Anzo","email":"","orcid":"","institution":"Kitasato University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuri","middleName":"","lastName":"Anzo","suffix":""},{"id":529092992,"identity":"6330b440-7093-4db8-9bfe-2601b6fb2dc1","order_by":9,"name":"Misaki Uchikawa","email":"","orcid":"","institution":"Kitasato University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Misaki","middleName":"","lastName":"Uchikawa","suffix":""},{"id":529092993,"identity":"bcb2b98b-6472-44a7-bb5c-73b6aa977872","order_by":10,"name":"Haruki Yamamoto","email":"","orcid":"","institution":"Kitasato University 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16:31:41","extension":"html","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":102001,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7701613/v1/fb2196f0335f0a3247be8600.html"},{"id":94483905,"identity":"d3315a95-b92a-4f4b-8c20-25024f7d2c07","added_by":"auto","created_at":"2025-10-27 16:31:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":5456859,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patient selection\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7701613/v1/8d2e30e58cfec3eb98692e49.png"},{"id":94483926,"identity":"4df2ac0e-26d7-45f0-9338-254c5df34a80","added_by":"auto","created_at":"2025-10-27 16:31:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1005365,"visible":true,"origin":"","legend":"\u003cp\u003eComplete response (CR) rates during the extended overall period (0–168 h) in the aprepitant (APR) and Fosnetupitant (F-NTP) groups\u003cbr\u003e\nThe F-NTP group demonstrated a significantly higher CR rate than did the APR group (83.5% vs. 69.4%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001, Fisher’s exact test).\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7701613/v1/4bce2cb214fe6ed97bc4f871.png"},{"id":94483800,"identity":"aa8c51f5-ae5b-4312-bbec-cd78549e040f","added_by":"auto","created_at":"2025-10-27 16:29:37","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2357052,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for time to treatment failure (TTF) in the APR and F-NTP groups\u003cbr\u003e\nTreatment failure was defined as the first episode of vomiting or the use of rescue medication. The F-NTP group demonstrated a significantly longer TTF than did the APR group (log-rank test; hazard ratio 0.48, 95% confidence interval (CI): 0.33-0.71, \u003cem\u003ep\u003c/em\u003e = 0.001, Cox proportional hazards model).\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-7701613/v1/ce6fad1282db3c2b6967d69a.png"},{"id":98245204,"identity":"1d41391d-cfda-4f3a-9c2c-756d288399bd","added_by":"auto","created_at":"2025-12-15 16:17:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":9775867,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7701613/v1/b2e77fb0-921a-4827-9f4b-65d8ff1c891e.pdf"}],"financialInterests":"","formattedTitle":"Sustained Antiemetic Efficacy of Fosnetupitant versus Aprepitant in Carboplatin-based Chemotherapy: A Retrospective Observational Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCarboplatin (CBDCA) is dosed according to the \u0026ldquo;Calvert formula,\u0026rdquo; where the dose is determined based on renal function and a target area under the concentration-time curve (AUC)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This dosing strategy allows CBDCA to have a more favorable toxicity profile than that of cisplatin, with a lower risk of renal impairment. Consequently, CBDCA is safe and effective (even in older adult patients and those with comorbidities) and has a common application in cancer chemotherapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCBDCA is traditionally classified as a moderately emetogenic chemotherapy (MEC) agent; however, accumulating evidence from clinical trials has prompted its reclassification as a highly emetogenic chemotherapy when administered at an AUC of \u0026ge;\u0026thinsp;4 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Therefore, guideline-recommended prophylaxis currently includes triple antiemetic therapy, comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT₃RA), dexamethasone, and a neurokinin-1 receptor antagonist (NK\u003csub\u003e1\u003c/sub\u003e RA). A randomized controlled trial (RCT) of patients with gynecologic cancer demonstrated that the addition of aprepitant (APR) to a standard regimen significantly improved the complete response (CR; defined as no emesis or use of rescue antiemetics during the observation period) rate for vomiting [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]; however, another study reported no significant benefits of APR when combined with palonosetron [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. A recent meta-analysis of 15 RCTs where approximately 60% of participants received CBDCA-containing MEC demonstrated that triple therapy significantly improved the CR and complete control rates compared with the effect of doublet therapy, supporting the utility of NK\u003csub\u003e1\u003c/sub\u003e RA addition in CBDCA-based regimens [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe use of intravenous fosaprepitant (F-APR), an NK\u003csub\u003e1\u003c/sub\u003e RA, has been limited in Japan. Retrospective observational studies have reported frequent vascular pain and phlebitis at the infusion site, prompting treatment modification to oral APR in approximately one quarter of patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and limiting its adoption. Fosnetupitant (F-NTP), a long-acting NK\u003csub\u003e1\u003c/sub\u003e RA, was approved in Japan in 2022. F-NTP has demonstrated non-inferiority to F-APR concerning CR during the 0\u0026ndash;120 h observation period after chemotherapy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Moreover, it recently demonstrated higher control rates than did conventional NK\u003csub\u003e1\u003c/sub\u003e Ras, even in the newly defined beyond-delayed phase (120\u0026ndash;168 h) introduced in the Japanese guidelines for appropriate antiemetic use [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, there are limited comparative studies involving the specific evaluation of NK\u003csub\u003e1\u003c/sub\u003e RAs in CBDCA-based regimens between an extended 0\u0026ndash;168-h observation period, including the beyond-delayed phase (Days 6\u0026ndash;7).\u003c/p\u003e\u003cp\u003eTherefore, we aimed to evaluate the antiemetic efficacy of NK\u003csub\u003e1\u003c/sub\u003e RAs between 1 week (0\u0026ndash;168 h) following chemotherapy by directly comparing F-NTP with APR. Treatment effects were particularly focused on during the underexplored beyond-delayed phase to clarify the clinical significance of F-NTP in CBDCA-based regimens.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Population\u003c/h2\u003e\u003cp\u003eThis single-center retrospective study included patients who received CBDCA-containing chemotherapy regimens at our institution between December 1, 2019, and March 31, 2024, and were administered an NK\u003csub\u003e1\u003c/sub\u003e RA as a prophylactic antiemetic therapy. The base-case population comprised patients who received intravenous F-NTP, and their responses and safety outcomes were compared with those of patients who received oral APR. Eligible patients had completed their first chemotherapy course, and all patients received triple antiemetic therapy containing a 5-HT₃ RA, dexamethasone, and an NK\u003csub\u003e1\u003c/sub\u003e RA.\u003c/p\u003e\u003cp\u003e This study was approved by the Ethics Committee of Kitasato University Hospital (approval number: B24-048) and conducted in accordance with the Declaration of Helsinki. Informed consent was obtained through an opt-out procedure.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eData on sex, age, Eastern Cooperative Oncology Group performance status, cancer type, disease stage, recurrence status, actual CBDCA dose, concomitant anticancer drugs, concomitant radiotherapy, alcohol consumption history, smoking history, and the concomitant use of olanzapine were collected from the electronic medical records. Chemotherapy-induced nausea and vomiting (CINV), constipation, and hiccups were assessed as treatment-related adverse events (AEs). CINV was evaluated for up to 168 h after the first chemotherapy administration, and the following endpoints were analyzed: the proportion of patients achieving CR and time to treatment failure (TTF, defined as the time to the first emetic episode or the use of rescue antiemetics). The extended overall period (0\u0026ndash;168 h) was further divided into acute (0\u0026ndash;24 h), overall (0\u0026ndash;120 h), extended-delayed (24\u0026ndash;168 h), and beyond-delayed (120\u0026ndash;168 h) phases. The AE severity was graded according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).\u003c/p\u003e\n\u003ch3\u003eEndpoints\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was the comparison of CR rates between the F-NTP and APR groups during the extended overall period (0\u0026ndash;168 h).\u003c/p\u003e\u003cp\u003eThe secondary endpoints included the CR rates during the acute (0\u0026ndash;24 h), overall (0\u0026ndash;120 h), extended-delayed (24\u0026ndash;168 h), and beyond-delayed (120\u0026ndash;168 h) phases; the identification of risk factors for non-CR; TTF; and the incidence and severity of treatment-related AEs such as constipation and hiccups.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eTo adjust for baseline differences between groups, propensity scores were calculated using five covariates: sex, age, alcohol consumption history, CBDCA dose, and the 5-HT₃ RA type that could influence the development of CINV. Subsequently, propensity score matching (1:1 nearest-neighbor method, caliper width\u0026thinsp;=\u0026thinsp;0.2) was performed. Baseline characteristics were compared using Fisher\u0026rsquo;s exact test for categorical variables, Mann\u0026ndash;Whitney U test for age, and Student\u0026rsquo;s t-test for CBDCA dose. In addition, Fisher\u0026rsquo;s exact test was used to compare the CR rates between the groups. To identify the factors associated with non-CR, univariate and multivariate logistic regression analyses were conducted using five covariates (sex, age, alcohol consumption, CBDCA dose, and F-NTP administration), and the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. TTF was analyzed using the Kaplan\u0026ndash;Meier method, and group differences were assessed using the log-rank test. All statistical analyses were performed using SPSS version 29 (IBM Corp., Armonk, NY, USA), and a \u003cem\u003ep-\u003c/em\u003evalue\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003ePatient Characteristics\u003c/h2\u003e\u003cp\u003eOf the 856 patients who received CBDCA-based chemotherapy regimens, 10 were excluded owing to inappropriate antiemetic administration. In addition, we excluded 18 participants owing to missing evaluation data, leaving 828 patients eligible for the analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Based on the prophylactic antiemetic regimen administered, 272 and 556 patients were assigned to the F-NTP and APR groups, respectively. Following propensity score matching, 242 patients were included in each group. The distributions of the propensity scores for the five matched factors before and after matching are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The other baseline characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Variables such as sex, age, alcohol consumption history, CBDCA dose, and the 5-HT₃ RA type were well balanced between groups.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eBefore propensity score matching\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eAfter propensity score matching\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAPR group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eF-NTP group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAPR group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eF-NTP group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;556)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;272)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;242)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;242)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.856\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e180 (32.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e161 (59.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e133 (55.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e136 (56.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e376 (67.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e111 (40.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e109 (45.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e106 (43.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003cp\u003e(median, range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66 (28\u0026ndash;91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73 (35\u0026ndash;89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e71 (28\u0026ndash;86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e72 (35\u0026ndash;88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.394\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlcohol habit, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e216 (38.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150 (55.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e130 (53.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e133 (55.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.855\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCBDCA dose\u003c/p\u003e\u003cp\u003eAUC, Average (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.39 (0.79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.21 (0.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.10 (0.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.21 (0.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.132\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5-HT\u003csub\u003e3\u003c/sub\u003e RA, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.926\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePalonosetron\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e146 (26.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e177 (65.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e146 (60.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e148 (61.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGranisetron\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e410 (73.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95 (34.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e96 (39.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e94 (38.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eF-NTP, fosnetupitant; APR, aprepitant; CBDCA, carboplatin; AUC, Area Under the Curve; 5-HT\u003csub\u003e3\u003c/sub\u003e RA, 5-hydroxytryptamine-3 receptor antagonist\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOther patient characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAPR group (N\u0026thinsp;=\u0026thinsp;242)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eF-NTP group (N\u0026thinsp;=\u0026thinsp;242)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG performance status, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e134 (55.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150 (62.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96 (39.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63 (26.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (7.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (4.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor type, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLung cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e137 (56.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e160 (66.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGynecological cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (19.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (15.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrothelial carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (10.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (9.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBreast cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (8.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer stage, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (3.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (3.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47 (19.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e117 (48.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e133 (55.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecurrence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (22.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46 (19.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConcomitant anticancer drugs, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e240 (99.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e231 (95.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModerate risk\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined with radiation, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (1.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (5.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking history, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e143 (59.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e162 (66.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProphylactic administration of olanzapine, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (2.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (1.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDose of dexamethasone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 1 Intravenous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68 (28.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44 (18.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e121 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91 (37.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e16.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (22.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38 (15.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e33.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 2 and after\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOral administration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61 (25.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (21.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntravenous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (10.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57 (23.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eF-NTP, fosnetupitant; APR, aprepitant; ECOG, Eastern Cooperative Oncology Group\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eCR Rate for Each Group\u003c/h3\u003e\n\u003cp\u003eThe CR rates during the extended overall period (0\u0026ndash;168 h) are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The CR rate during this period was significantly higher in the F-NTP group than in the APR group (83.5% vs. 69.4%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes the patient populations that achieved CR at each time point. F-NTP achieved significantly higher CR rates than did APR during the acute (0\u0026ndash;24 h; 99.6% vs. 94.2%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), overall (0\u0026ndash;120 h; 88.4% vs. 74.4%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and extended delayed (24\u0026ndash;168 h; 83.5% vs. 69.4%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) phases. In contrast, the CR rates during the beyond-delayed phase (120\u0026ndash;168 h) were significantly higher in the APR group than in the F-NTP group (93.8% vs. 86.4%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of CR rates between APR and F-NTP\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAPR group (N\u0026thinsp;=\u0026thinsp;242)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eF-NTP group (N\u0026thinsp;=\u0026thinsp;242)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute (0\u0026ndash;24 h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e94.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e99.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall (0\u0026ndash;120 h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e74.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e88.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtended-delayed (24\u0026ndash;168 h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e69.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e83.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeyond-delayed (120\u0026ndash;168 h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e93.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e86.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eCR, complete response; F-NTP, fosnetupitant; APR, aprepitant\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eExamination of Risk Factors\u003c/h3\u003e\n\u003cp\u003eIn real-world practice, the effect of patient characteristics on CINV control and anticancer efficacy is partially understood. Therefore, we evaluated the effect of F-NTP on CR while adjusting for clinically significant confounders. The univariate and multivariate analyses of the risk factors for non-CR during the extended overall period (0\u0026ndash;168 h) are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of CR rates between APR and F-NTP\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eMultivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.60\u0026ndash;3.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.35\u0026ndash;3.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.95\u0026ndash;0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.95\u0026ndash;0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlcohol habit, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.55\u0026ndash;1.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.396\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.62\u0026ndash;1.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.936\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCBDCA dose (AUC)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.10\u0026ndash;2.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.11\u0026ndash;1.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eF-NTP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.29\u0026ndash;0.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.27\u0026ndash;0.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eCR, complete response; F-NTP, fosnetupitant; APR, aprepitant; CBDCA, carboplatin; AUC, Area Under the Curve\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the univariate analysis, female sex, younger age, and high CBDCA dose were significantly associated with non-CR, whereas F-NTP administration was associated with a reduced non-CR risk. However, alcohol consumption showed no significant association.\u003c/p\u003e\u003cp\u003eIn the multivariate analysis including all candidate risk factors, female sex increased the non-CR risk by approximately two-fold (OR, 2.18; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Age was protective, with each additional year reducing the non-CR risk by approximately 3% (OR, 0.97; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009). A high CBDCA dose increased the risk, with an OR of 1.47 per 1-unit increase in the AUC (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008). The use of F-NTP was identified as an independent factor that significantly reduced non-CR risk compared with the APR effect (OR, 0.42; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similar to the event in the univariate analysis, alcohol consumption showed no significant association in the multivariate analysis.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eTTF\u003c/h2\u003e\u003cp\u003eThe Kaplan\u0026ndash;Meier curves are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The log-rank test revealed that TTF was significantly longer in the F-NTP group than in the APR group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). At 168 h, the median TTF was not reached in the F-NTP group, whereas it was reached at 120 h in the APR group. Notably, the curves diverged early in the delayed phase (24\u0026ndash;120 h), suggesting a lower incidence of CINV in the F-NTP group. The Cox proportional hazards model demonstrated that F-NTP reduced the risk of treatment failure by approximately 52% compared with the effect of APR (hazard ratio [HR]: 0.48; 95% CI: 0.33\u0026ndash;0.71).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eAEs\u003c/h2\u003e\u003cp\u003eThe incidence of AEs is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Constipation occurred in 59.5% of the F-NTP group participants and in 57.9% of those in the APR group, implying no significant differences (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.712). Most cases were Grade 1 or 2, and only one case of Grade 3 constipation (0.4%) was observed in the F-NTP group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of the incidence of adverse events between the F-NTP and F-APR groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAPR group (N\u0026thinsp;=\u0026thinsp;242)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eF-NTP group (N\u0026thinsp;=\u0026thinsp;242)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConstipation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e140 (57.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e144 (59.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.782\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e116 (47.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e122 (50.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHiccup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18 (7.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eF-NTP, fosnetupitant; APR, aprepitant\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eHiccups occurred in 7.4% of the participants in the F-NTP group and in 12.4% of those in the APR group, showing a lower trend with F-NTP treatment but without statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.094). Most hiccup events were Grade 1 or 2; only one Grade 3 hiccup event (0.4%) occurred in the F-NTP group.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the first study on the direct comparison of F-NTP and APR potentials to prevent CINV between 1 week (0\u0026ndash;168 h) following CBDCA-based chemotherapy. Evident imbalances in baseline characteristics existed between the two groups; thus, we applied propensity score matching to minimize confounding factors. The CR rate during the extended overall period (0\u0026ndash;168 h) was significantly higher in the F-NTP group than in the APR group. Notably, the curves for treatment success began to diverge early in the delayed phase (24\u0026ndash;120 h), highlighting the sustained antiemetic efficacy of F-NTP. Although the CR rate of the APR group slightly exceeded that of the F-NTP group in the beyond-delayed phase (120\u0026ndash;168 h), the F-NTP group demonstrated superior long-term efficacy. Furthermore, in the multivariate analysis, F-NTP therapy emerged as an independent predictor of a reduced non-CR risk (OR, 0.42). In addition, TTF analysis revealed that the risk of treatment failure was reduced by approximately 53% in the F-NTP group compared with that in the APR group (HR, 0.47), and this effect persisted up to 168 h. These findings support the long-term efficacy of F-NTP in patients receiving CBDCA-based regimens.\u003c/p\u003e\u003cp\u003eDuring the extended overall phase (0\u0026ndash;168 h), the F-NTP group achieved a CR rate of 83.5%, compared with 69.4% in the APR group. These results are consistent with the findings of previous studies on patients receiving cisplatin (CDDP)-based regimens [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and may be partly explained by the pharmacokinetic properties of F-NTP. The terminal half-life of the active metabolite of APR in healthy volunteers was 13.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8 h [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], whereas that of F-NTP was markedly longer (70.4\u0026thinsp;\u0026plusmn;\u0026thinsp;22.3 h) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Moreover, in real-world settings, where patients are older than those enrolled in clinical trials, adherence concerns with orally administered drugs such as APR may further contribute to the differences in efficacy between APR and intravenous regimens pre-integrated with F-NTP or fosaprepitant (F-APR) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eDuring the beyond-delayed phase (120\u0026ndash;168 h), APR achieved a higher CR rate (93.8%) than did F-NTP (86.4%). There are several possible explanations for the discrepancy. Patients who required rescue medication during the delayed phase (24\u0026ndash;120 h) were more in the APR group than in the F-NTP group, which may have subsequently suppressed CINV during the beyond-delayed phase. Conversely, because patients in the F-NTP group achieved favorable control in the extended overall period, the use of rescue medication was limited, possibly resulting in a decline in antiemetic protection in the beyond-delayed phase. Additionally, the relatively large sample size in this study may have facilitated the detection of statistically significant differences, even when the actual clinical differences between the groups were small. Beyond these considerations, the temporal pattern of efficacy observed in our study differs from those in previous reports on CDDP-based regimens. CDDP shows a slower increase and a more sustained plasma concentration of free platinum, prolonging emetogenic stimulation and usually leading to larger differences in the beyond-delayed phase [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In contrast, CBDCA exhibits a rapid increase and earlier disappearance, resulting in a higher emetogenic risk during the acute and early delayed phases, but a diminished impact in the beyond-delayed phase [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Consequently, group differences in CBDCA were most evident in the early period, whereas in the beyond-delayed phase, patient-related factors may have played a more dominant role in determining the outcomes.\u003c/p\u003e\u003cp\u003eTo explore the risk factors for CINV, we analyzed five variables (sex, age, alcohol intake, CBDCA dose, and F-NTP use) using univariate and multivariate models based on previous reports [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Female sex, younger age, and a high CBDCA dose were confirmed as significant risk factors for non-CR, consistent with previous reports. In contrast, alcohol consumption was not a significant factor, possibly because the retrospective design precluded the accurate quantification of drinking habits from clinical records. Notably, F-NTP use emerged as an independent predictor of a reduced non-CR risk.\u003c/p\u003e\u003cp\u003eKaplan\u0026ndash;Meier curves revealed that the F-NTP group differed early from the APR group, maintaining higher event-free rates for 168 h. This visual and statistical concordance indicates that F-NTP prolonged treatment success. The difference was particularly pronounced between 24 and 120 h, which appeared to be the primary driver of the overall difference. Two factors could explain this observation. The first condition is the pharmacological characteristics of CBDCA. The rapid increase of CBDCA in free platinum concentration provides strong emetogenic stimulation from the acute phase onward [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In contrast to the reports on CDDP-based regimens [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], where differences usually emerge later in the delayed phase, effective early control during the acute and early delayed phases appears critical in CBDCA regimens, and F-NTP may provide this advantage. The second factor is the receptor occupancy profile of F-NTP. Following intravenous administration, F-NTP undergoes rapid conversion to its active metabolite, achieving high NK₁ receptor occupancy promptly and sustaining it over time [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In contrast, APR, administered orally, is subject to absorption and distribution delays, and its receptor occupancy gradually declines [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Thus, in addition to \u0026ldquo;duration,\u0026rdquo; the \u0026ldquo;rapidity\u0026rdquo; of NK₁ receptor blockade by F-NTP may align more closely with the early emetogenic challenge of CBDCA, accounting for its superiority in the acute to early delayed phases. NK₁ RAs have been traditionally emphasized for their persistence; however, our findings suggest that onset and potency constitute key determinants of CINV control.\u003c/p\u003e\u003cp\u003eRegarding AEs, the typical side effects of NK₁RAs include hiccups and constipation, which, if severe, may trigger nausea and vomiting. Therefore, careful monitoring is necessary. In this study, the incidence of AEs showed no significant differences between the F-NTP and APR groups. Moreover, most events were Grade 1 in both groups, and no critical AEs were reported, indicating the favorable tolerability of both agents.\u003c/p\u003e\u003cp\u003eThis study has some limitations. First, it relied on retrospectively collected data from a single center, and the residual bias from patient background may not have been fully eliminated; thus, we applied propensity score matching to account for major confounders. Second, information on certain risk factors previously reported for CINV, such as a history of hyperemesis gravidarum or motion sickness, was unavailable in our dataset, which may have influenced our results.\u003c/p\u003e\u003cp\u003eF-NTP demonstrated superior CINV control compared with that of APR during an extended overall period (0\u0026ndash;168 h) in patients receiving CBDCA-based chemotherapy. F-NTP was associated with a significant reduction in nausea and vomiting without causing severe AEs and was well tolerated. These findings support the clinical utility of F-NTP in CBDCA-based regimens.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConflict of Interest:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eThis study received no funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Availability\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics Approval:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eThis study was approved by the Ethics Committee of Kitasato University Hospital (approval number: B24-048) and conducted in accordance with the Declaration of Helsinki. Informed consent was obtained through an opt-out procedure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor contributions\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003eConceptualization: Hiroshi Inano; Data curation: Hiroshi Inano; Formal Analysis: Yoshihito Morimoto; Funding acquisition: Hiroshi Inano; Investigation: Atsushi Kawamura, Taichi Ikegami, Tomoki Niizuma, Kanata Kitagawa, Rie Usami, Kozue Nakagomi, Yuri Anzo, Misaki Uchikawa; Methodology: Hiroshi Inano; Project administration: Hiroshi Inano; Resources: Hiroshi Inano; Software: Hiroshi Inano; Supervision: Katsuya Otori; Validation: Hiroshi Inano; Visualization: Yoshihito Morimoto; Writing – original draft: Hiroshi Inano; Writing – review \u0026amp; editing: Yoshihito Morimoto, Haruki Yamamoto, Aiko Shono, Kazuhiro Watanabe. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments:\u003c/h2\u003e\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSchwenk MH (2024) Carboplatin Dosing on the Basis of Renal Function: 30+ Years after Calvert. Kidney360 5:271-273. https://doi.org/10.34067/KID.0000000000000349\u003c/li\u003e\n\u003cli\u003eAogi K, Takeuchi H, Saeki T et al (2021) Optimizing antiemetic treatment for chemotherapy-induced nausea and vomiting in Japan: Update summary of the 2015 Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis. Int J Clin Oncol 26:1-17. https://doi.org/10.1007/s10147-020-01818-3\u003c/li\u003e\n\u003cli\u003eIihara H, Abe M, Wada M et al (2024) 2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis. Int J Clin Oncol 29:873-888. https://doi.org/10.1007/s10147-024-02535-x\u003c/li\u003e\n\u003cli\u003eYahata H, Kobayashi H, Sonoda K et al (2016) Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin. Int J Clin Oncol 21:491-497. https://doi.org/10.1007/s10147-015-0928-y\u003c/li\u003e\n\u003cli\u003eWatanabe Y, Saito Y, Mitamura T, Takekuma Y, Sugawara M (2021) Adding aprepitant to palonosetron does not decrease carboplatin-induced nausea and vomiting in patients with gynecologic cancer. 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Accessed September 13, 2025\u003c/li\u003e\n\u003cli\u003eSpandidos DA, Pintzas A, Kakkanas A, Yiagnisis M, Mahera H, Patra E, Agnantis NJ (1987) Elevated expression of the myc gene in human benign and malignant breast lesions compared to normal tissue. Anticancer Res 7:1299-1304.\u003c/li\u003e\n\u003cli\u003eInui N, Toi Y, Yoneshima Y, Morise M, Hata A, Kubota K, Saeki T, Tamura T (2023) Pooled Analysis of Studies Evaluating Fosnetupitant and Risk Factors for Cisplatin-Induced Nausea and Vomiting During the Extended Overall Phase. Adv Ther 40:4928-4944. https://doi.org/10.1007/s12325-023-02648-1\u003c/li\u003e\n\u003cli\u003eCalvert AH, Newell DR, Gumbrell LA, O\u0026apos;Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME, Wiltshaw E (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748-1756. https://doi.org/10.1200/JCO.1989.7.11.1748\u003c/li\u003e\n\u003cli\u003eSpinelli T, Calcagnile S, Giuliano C, Rossi G, Lanzarotti C, Mair S, Stevens L, Nisbet I (2014) Netupitant PET imaging and ADME studies in humans. J Clin Pharmacol 54:97-108. https://doi.org/10.1002/jcph.198 \u003c/li\u003e\n\u003cli\u003eLasseter KC, Gambale J, Jin B, Bergman A, Constanzer M, Dru J, Han TH, Majumdar A, Evans JK, Murphy MG (2007) Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol 47:834-840. https://doi.org/10.1177/0091270007301800\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Fosnetupitant, CINV, NK1 RA, CBDCA, beyond-delayed","lastPublishedDoi":"10.21203/rs.3.rs-7701613/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7701613/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCarboplatin (CBDCA) is highly emetogenic when administered at an area under the curve (AUC) ≥4, requiring triple antiemetic therapy, including an NK\u003csub\u003e1\u003c/sub\u003e receptor antagonist (NK\u003csub\u003e1 \u003c/sub\u003eRA). Fosnetupitant (F-NTP), a long-acting NK\u003csub\u003e1 \u003c/sub\u003eRA, may provide sustained receptor occupancy; however, its \u0026nbsp;direct comparisons with aprepitant (APR) in CBDCA-based regimens between 0-168 h remain lacking. We aimed to evaluate the antiemetic efficacy of F-NTP versus APR between 1 week following chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective single-center observational study included patients with cancer receiving CBDCA (AUC ≥4)-based regimens. Propensity score matching was performed using clinical factors. The primary endpoint was complete response (CR; no emesis or rescue medication) rate between 0–168 h. The secondary endpoints included phase-specific CR rates, time to treatment failure (TTF), and adverse events (AEs).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAfter matching, 242 patients were included in each group. The overall CR rate at 0–168 h was significantly higher with F-NTP (83.5%) than with APR (69.4%) (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). F-NTP significantly prolonged TTF (hazard ratio =0.48, 95% confidence interval: 0.33–0.71, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). Multivariate analysis revealed female sex, younger age, and high CBDCA dose as significant risk factors for non-CR, while F-NTP use was a protective factor. AEs did not differ significantly between the groups and were mostly Grade 1.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eF-NTP demonstrated superior antiemetic efficacy to that of APR in CBDCA-based regimens, particularly maintaining higher CR rates through the acute and delayed phases. F-NTP was also well tolerated, supporting its potential as a strong prophylactic agent for preventing chemotherapy-induced nausea and vomiting.\u003c/p\u003e","manuscriptTitle":"Sustained Antiemetic Efficacy of Fosnetupitant versus Aprepitant in Carboplatin-based Chemotherapy: A Retrospective Observational Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-27 16:02:04","doi":"10.21203/rs.3.rs-7701613/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions","date":"2025-10-29T03:36:03+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-10-13T23:48:48+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-13T23:26:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-27T02:42:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2025-09-24T05:03:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a679acd4-2b76-46c0-aaa1-fde0f719aca8","owner":[],"postedDate":"October 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:12:26+00:00","versionOfRecord":{"articleIdentity":"rs-7701613","link":"https://doi.org/10.1007/s10147-025-02940-w","journal":{"identity":"international-journal-of-clinical-oncology","isVorOnly":false,"title":"International Journal of Clinical Oncology"},"publishedOn":"2025-12-09 15:58:58","publishedOnDateReadable":"December 9th, 2025"},"versionCreatedAt":"2025-10-27 16:02:04","video":"","vorDoi":"10.1007/s10147-025-02940-w","vorDoiUrl":"https://doi.org/10.1007/s10147-025-02940-w","workflowStages":[]},"version":"v1","identity":"rs-7701613","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7701613","identity":"rs-7701613","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}