Adherence to High Cost Oral Antineoplastic Drugs in Oncological Patients of Arturo López Pérez Foundation Oncological Institute: An Observational Study

Adherence to High Cost Oral Antineoplastic Drugs in Oncological Patients of Arturo López Pérez Foundation Oncological Institute: An 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 Adherence to High Cost Oral Antineoplastic Drugs in Oncological Patients of Arturo López Pérez Foundation Oncological Institute: An Observational Study Claudia Chávez Oyanadel, Macarena Manríquez-Mimica, Romina A. Vargas Aránguiz, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7786354/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract BACKGROUND Cancer remains a major global public health challenge, with incidence and treatment costs steadily increasing. The use of oral antineoplastic drugs (OAD) has expanded due to their convenience and positive impact on patients’ quality of life, but ensuring optimal adherence remains a critical issue. Non-adherence can compromise treatment effectiveness, increase healthcare costs, and worsen clinical outcomes. This study aimed to evaluate adherence to high-cost oral anticancer drugs (HCOADs) among oncological patients from Arturo López Pérez Foundation Oncological Institute, and to explore its association with demographic and clinical characteristics as well as progression-free survival (PFS). METHODS A prospective observational study was designed with a 12-month follow-up period. Patients enrolled in the Oncological Insurance (OI) of Arturo López Pérez Foundation Oncological Institute who received HCOADs between 2020 and 2021 were included. Adherence was assessed monthly through the telephone administration of the Simplified Medication Adherence Questionnaire (SMAQ). Demographic and clinical variables, as well as relevant clinical outcomes (disease progression, adverse events, and mortality), were collected. Descriptive and survival analyses (Kaplan–Meier) were performed RESULTS Out of ninety-two eligible patients, forty-nine participated in the study (53.3%). All participants maintained full adherence throughout the follow-up period. However, 36.7% experienced disease progression, 4.1% developed treatment-related toxicity, and 4.1% died. The 12-month PFS rate was 50%. A marked increase in progression was observed after the seventh month. No statistically significant associations were found between adherence and clinical outcomes. CONCLUSION Full adherence may be influenced by financial support and personalized follow-up. Nevertheless, the observed disease progression suggests that adherence alone is not sufficient to ensure favorable outcomes. A comprehensive approach that incorporates additional clinical and social determinants is warranted. Medication Adherence Antineoplastic Agents Cancer Treatment Progression-Free Survival Patient Support Figures Figure 1 BACKGROUND Cancer represents a major public health problem worldwide, both in terms of magnitude and the burden of disease it entails, and incidence rates have continued to rise in most countries since 1990 ( 1 ). Advances in cancer treatment have been significant, particularly in recent years, becoming more specific, more personalized, and less invasive, which results in a better quality of life for patients. However, these improvements also require large investments and generate high personal, family, and state costs. High-Cost Drugs (HCD) is a concept that may vary depending on the context in which it is used, but what all definitions have in common is that they demand an increasing volume of financial resources. In Chile, the most recent decree ( 2 ) established a national annual cost threshold for a high-cost treatment of 3.270 USD (Decree eighty-six, Law 20.850). In general, the administration of oral antineoplastic drugs (OAD) has accelerated in both curative and palliative settings. Therefore, the development of effective strategies to promote optimal adherence to cancer medication regimens has become a priority. The major advantages of OAD use are the level of independence and reduction of healthcare costs due to outpatient treatment ( 3 , 4 ). Additionally, OAD offers benefits for patients such as greater convenience and less time away from home, which improves quality of life compared to intravenous treatment. However, adherence is more difficult to monitor, as are the adverse effects of the treatment ( 5 ). There are several definitions regarding the meaning of “treatment adherence,” with no consensus on how it should be measured or approached. For the purposes of this study, we considered the World Health Organization (WHO) definition, which states that adherence is the extent to which a patient’s behavior in relation to medication intake corresponds with the agreed recommendations from a healthcare professional ( 6 ). Among the factors studied that impact positive treatment adherence are patients’ knowledge about their diagnosis and treatment, as well as their perception of the medication as beneficial and necessary for their health ( 3 ). A key facilitator of medication adherence is patient motivation. If a patient is aware of the drug’s benefits and necessity, their motivation will increase. Support from friends, family, and co-workers also fosters medication adherence ( 7 ). On the contrary, non-adherence to treatment increases the disease burden and leads to negative consequences, resulting in higher treatment failure rates, greater hospitalization rates, and consequently higher healthcare costs ( 8 , 9 , 10 ). A qualitative study in breast cancer patients observed that good communication and adequate information are the most critical factors in facilitating better treatment adherence ( 11 ). Adequate therapeutic adherence has been shown to improve disease prognosis, in addition to strengthening appropriate control measures for allocating resources in prevention, diagnosis, treatment, palliative care, and monitoring effectiveness ( 1 , 5 ). Despite the significant advances in therapeutic management and comprehensive treatment of oncological diseases, the current concern is the lack of treatment adherence. The main causes identified are drug-related adverse effects, the high costs involved, the complexity of therapeutic regimens, and the multiple food-drug and drug-drug interactions ( 12 ). According to the literature, adherence rates to OAD vary widely depending on the population, cancer type, and measurement method ( 5 ). It is estimated that between 20% and 50% of patients do not adhere to prescribed treatment regimens, indicating that they “do not comply” or “do not adhere” to therapy ( 13 ). The Arturo López Pérez Foundation Oncological Institute (FALP, by its acronym in Spanish), is a comprehensive cancer care center located in Santiago, Chile, which treats an average of 3,000 patients per year from across the country. In addition to providing highly complex oncological treatments, including surgery, radiotherapy, and systemic therapies. FALP has a solidarity-based health financing system currently covering more than one million beneficiaries through a monthly contribution. This solidarity financing, called “Convenio Oncológico” (Oncological Insurance, OI), covers the copayment of all services related to treatment and follow-up received at FALP for any type of cancer, with no coverage caps or event limits. There is also an HCD Committee, composed by a Health Technology Assessment Unit and specialists in the field, which evaluates potential beneficiaries for these medications. Moreover, the OI population is highly diverse in terms of geographic distribution, age range, and oncological diagnosis; this is also reflected in the beneficiaries of HCOADs. However, we are unaware whether these variables influence or are associated with greater or lesser treatment adherence. METHODS The aim of this study was to estimate adherence to prescribed high-cost oral antineoplastic drugs among patients affiliated to the Arturo López Pérez Foundation Oncological Institute, to describe their demographic and clinical characteristics, and to assess whether therapeutic adherence impacts progression-free survival. An observational, prospective study was conducted with a follow-up period of twelve months. This study was approved by the Scientific Ethics Committee of FALP, which is accredited in accordance with current local legislation (code No. 2020-037-QUA-SIN-INT). The target population consisted of OI affiliates over 18 years of age who received HCOADs financing for their oncological treatment during 2020–2021. Data collection was performed using the Simplified Medication Adherence Questionnaire (SMAQ), adapted for use in cancer patients ( 14 ). This instrument has been validated in several countries ( 15 , 16 ) and has the advantage of being a brief, simple, cost-effective, and easy-to-administer method; however, it may overestimate adherence, presenting a low negative predictive value ( 14 ). Patients meeting the selection criteria were contacted by phone and invited to participate in the study. Only those who expressed interest were sent an Informed Consent Form via email, explaining the study’s objectives and implications, and informing them about the confidentiality and voluntariness of their participation. The SMAQ questionnaire was administered by phone on a monthly basis (30 ± 4 days). Participants were contacted by the same OI coordinator, who was previously trained in administering the instrument. The date of study entry was considered as the date of the first telephone interview. Patients were contacted until the end of follow-up, defined as 12 months post first interview, or disease progression as reported by a physician upon new findings, or withdrawal of consent, or death, whichever occurred first. Other variables measured included demographic data (sex, age, insurance, and region), oncological diagnosis, type of HCOADs used, and drug-related toxicity, defined as a change in therapy by the treating physician due to a clinically significant adverse event or an event that incapacitated the patient for any other reason. Statistical Analysis An exploratory analysis of the results was performed using tables and graphs. For categorical variables, proportions with their 95% confidence intervals were calculated, while quantitative data were expressed as medians and interquartile ranges (IQR, corresponds to the range between the 25th and 75th percentiles). To evaluate bivariate associations, the Student’s t-test and Kruskal-Wallis test were used for quantitative variables, and the chi-square test or Fisher’s exact test were used for categorical variables, depending on the nature of the data. Survival was calculated from the date of the first interview until the date of death or censoring, considering censoring for loss to follow-up due to progression or toxicity. The final status variable was used to define the states, in order to exclude from the survival curve those patients who died after the end of the study. Survival curves were estimated using the Kaplan-Meier method, and differences in survival between groups were assessed using the log-rank test. A p-value less than 0.05 was considered statistically significant. Statistical analyses were performed using R software version 4.4.2. RESULTS During the years 2020 and 2021, ninety-two patients were beneficiaries of HCOADs, 65.2% women (n = 60) and 34.8% men (n = 32), with a median age of 60.5 years (IQR 15.5 years). The most frequent oncological diagnoses were breast cancer, accounting for 33.7% (n = 31), and lung cancer, with 28.3% (n = 26) (Table 1 ). Table 1 Demographic and clinical characteristics of HOCADs beneficiary patients Characteristics Patients (%) (n) Sex Male 34,8% (n = 32) Female 65,2% (n = 60) Age Median: 60,5 years IQR: 15,5 years Oncological diagnosis Breast cancer 33,7% (n = 31) Lung cancer 28,3% (n = 26) Kidney cancer 15,2% (n = 14) Hematologic cancers 13,0% (n = 12) Prostate cancer 4,3% (n = 4) Ovarian cancer 3,3% (n = 3) Skin cancer 2,2% (n = 2) Summarizes the demographic (sex, age) and clinical (oncological diagnosis) characteristics of patients receiving High-Cost Oral Antineoplastic Drugs (HOCADs). Categorical variables are presented as percentages (n); continuous variables are reported as median and interquartile range (IQR). Abbreviations: HOCADs, High-Cost Oral Antineoplastic Drugs; IQR, Interquartile Range. Of these ninety-two patients, forty-nine (53.3%) agreed to participate in the study. The sex distribution showed that 69.4% (n = 34) were women and 30.6% (n = 15) were men, with a median age of 59 years (IQR 16 years). Patients mainly came from Region Metropolitana (30.6%, n = 15), followed by Biobío (12.2%, n = 6) and Valparaíso (10.2%, n = 5); only the regions of Aysén and Los Ríos had no cases. Regarding health insurance, 67.3% (n = 33) were affiliated with private health insurance providers, while 32.7% (n = 16) were affiliated with the public health insurance system. The most frequent diagnoses were breast cancer at 38.8% (n = 19), lung cancer at 20.4% (n = 10), and hematologic cancers combined at 14.3% (n = 6). Regarding the drugs used, Ribociclib was the most common at 32.7% (n = 16), followed by Everolimus at 12.2% (n = 6), and Osimertinib and Afatinib each at 10.2% (n = 5), which corresponded to the associated diagnoses (Table 2 ). Table 2 Demographic and clinical characteristics of study participants Characteristics Patients (%) (n) Sex Male 30,6% (n = 15) Female 69,4% (n = 34) Age Median: 59 years IQR: 16 years Region Arica y Parinacota 2% (n = 1) Tarapacá 2% (n = 1) Antofagasta 2% (n = 1) Atacama 4,1% (n = 2) Coquimbo 6,1% (n = 3) Valparaíso 10,2% (n = 5) Metropolitana 30,6% (n = 15) O’Higgins 4,1% (n = 2) Maule 6,1% (n = 3) Ñuble 6,1% (n = 3) Biobío 12,2% (n = 6) La Araucanía 6,1% (n = 3) Los Ríos 0% (n = 0) Los Lagos 4,1% (n = 2) Aysén 0% (n = 0) Magallanes 4,1% (n = 2) Summarizes the demographic (sex, age, and region) characteristics of the study participants who were receiving High-Cost Oral Antineoplastic Drugs (HOCADs). Categorical variables are presented as percentages (n); continuous variables are reported as median and interquartile range (IQR). Regions correspond to first-level administrative divisions of Chile. Abbreviations: HOCADs, High-Cost Oral Antineoplastic Drugs; IQR, Interquartile Range. In terms of adherence, all participating patients remained in the study until the end of follow-up (100% adherence). However, various outcomes were observed during the study, including disease progression, toxicity, and death. Specifically, 36.7% (n = 18) experienced disease progression, 4.1% (n = 2) experienced toxicity, and 4.1% (n = 2) died during follow-up. The median age of the patients who experienced progression was sixty-one years, while the median age of patients who remained on treatment until the end of follow-up was fifty-five years; however, this difference was not statistically significant (p = 0.1327). The most represented diagnoses among patients with progression were breast cancer at 44.4% (n = 8) and lung cancer at 22.2% (n = 4). Deaths occurred in patients with prostate cancer (n = 1) and kidney cancer (n = 1). No statistically significant differences were found between diagnosis and final status at follow-up (p = 0.6482). The most frequently used drugs in the progression group were Ribociclib at 38.9% (n = 7), and Everolimus and Osimertinib at 16.7% each (n = 3). In the treatment group, Ribociclib at 33.3% (n = 9) and Dasatinib at 18.5% (n = 5) were the most common drugs, while in the deceased patients group, Enzalutamide (n = 1) and Sunitinib (n = 1) were used. However, no significant differences were found between these variables (p = 0.08496). When calculating the 12-month progression-free survival, it was 0.5, meaning that the probability of these patients experiencing disease progression by month 12 was 50%. The survival curve shows that during the first seven months, the probability of progression is low and stable; however, after this period, the risk of progression increases and becomes more pronounced. This difference was statistically significant (p = 0.00000) (Fig. 1 ). DISCUSSION In contrast to other studies ( 13 ), all patients adhered to the treatments prescribed by their treating physician during the follow-up period in this study. This finding can be attributed to several key factors. First, the financial coverage provided to patients for medication costs played a crucial role. Another relevant factor was the constant monthly communication with patients. This strategy allowed not only a continuous reminder regarding treatment adherence but also the opportunity to address questions related to symptoms associated with treatment use and other administrative matters. Patients reported that the regular calls helped them feel supported and valued, which could have contributed to the observed adherence. As highlighted in other studies ( 7 , 11 ), this reinforces the importance of communication in managing adherence. Regarding toxicity, the results showed that the therapies administered did not cause serious or severe adverse effects, and only two patients in the cohort experienced side effects, but they continued adhering to the treatment. This may have contributed to fewer interruptions in their treatment, maintaining their adherence until the end of the study. This contrasts with findings in the literature ( 12 ), where toxicity is considered a significant risk factor for maintaining adherence. Despite full adherence, disease progression occurred in 36.7% of patients during the study. These results suggest that therapeutic adherence may be relevant, but it is not necessarily a guarantee that the disease will not progress. This could be explained by other variables not measured in this study, such as disease stage, genetic load of the patients, and other comorbidities, which could be part of future research based on these findings. On the other hand, based on progression-free survival results, we noted that although the disease remained stable at the beginning of the treatment, by the seventh month, the risk of progression increased sharply, which underscores the importance of constant monitoring in these patients during treatment ( 7 , 11 ). It is important to note that adherence, toxicity, and progression are not completely pure variables, as HCOADs are generally administered in combination with other therapies, such as cytotoxic chemotherapy or radiotherapy. Therefore, the results should be interpreted with caution, as the influence of these other therapies may have affected the outcomes. Another point worth mentioning, although it was not the primary objective of this study, is that all patients expressed disappointment at the end of their follow-up in the study. Many thanked the calls, and some even asked if they could continue contacting the executive to resolve future questions, which highlights the value of a personalized and close approach in oncological treatment. CONCLUSIONS This study provides valuable insights from a real-world context regarding adherence to oncological medications. The findings suggest that a combination of financial support, continuous communication and an environment that values patients’ needs can have a positive impact on treatment adherence. These results pave the way for further research on how to optimize support for oncology patients in clinical practice. Abbreviations OAD oral antineoplastic drugs HCOADs high-cost oral anticancer drugs PFS progression-free survival OI Oncological Insurance SMAQ Simplified Medication Adherence Questionnaire HCD High-Cost Drugs WHO World Health Organization FALP Arturo López Pérez Foundation Oncological Institute IQR Interquartile ranges Declarations Ethics approval and consent to participate: This study was approved by the Scientific Ethics Committee of Fundación Arturo Benitez, which is accredited in accordance with current local legislation (code No. 2020-037-QUA-SIN-INT). Consent for publication: Not applicable. Availability of data and materials: The datasets generated and analysed during the current study are not publicly available due to Chilean Law N° 19.628, the “Law on Protection of Private Life,” which regulates the processing of personal data and protects sensitive information, but are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: This research received no specific grant from any funding agency, commercial, or not-for-profit sectors. Authors' contributions Conceptualization: CCHO, MMM. Methodology: CCHO, MMM. Data curation: RVA, DMH. Formal Analysis: CCHO. Writing – Original Draft, Writing – Review & Editing, Visualization: CCHO, MMM, MHC. All authors gave final approval for all aspects of the work. Acknowledgements This work benefited from the collaboration of the FALP´s solidarity-based health financing system “Convenio Oncológico” with special acknowledgment to Ms. Ingrid Wullfrodt, who provided continuous and compassionate support to the patients throughout the study. References Fitzmaurice C, Dicker D, Pain A, et al. The global burden of cancer 2013. JAMA Oncol. 2015 Jul;1(4):505–27. PMID: 26181261. Library of the National Congress. Law No. 20.850: Establishes a Financial Protection System for High-Cost Diagnoses and Treatments [Internet]. Santiago: Library of the National Congress; [cited 2025 Aug 26]. Available from: https://www.bcn.cl/leychile/navegar?idNorma=1078148 Rosenberg SM, Petrie KJ, Stanton AL, Ngo L, Finnerty E, Partridge AH, et al. Interventions to enhance adherence to oral antineoplastic agents: a scoping review. J Natl Cancer Inst. 2020 May 1;112(5):443-65. PMID: 31899790. doi:10.1093/jnci/djz244. Mueller-Schöll A, Groenland SL, Scherf-Clavel O, van Dyk M, Huisinga W, Michelet R, et al. Therapeutic drug monitoring of oral targeted antineoplastic drugs. Eur J Clin Pharmacol. 2021 Apr;77(4):441–64. PMID: 33165648. doi:10.1007/s00228-020-03014-8. Olivera-Fernández R, Fernández-Ribeiro F, Piñeiro-Corrales G, Crespo-Diz C. Adherencia al tratamiento antineoplásico oral. Farm Hosp. 2014 Nov 3;38(6):475-81. PMID: 25542658. doi:10.7399/fh.2014.38.6.8061. Sabaté E, editor. Adherence to long-term therapies: Evidence for action [Internet]. Geneva: World Health Organization; 2003. 196 p. [cited 2025 Aug 26]. Available from: https://apps.who.int/iris/bitstream/handle/10665/42682/9241545992.pdf Kvarnström K, Westerholm A, Airaksinen M, Liira H. Factors contributing to medication adherence in patients with a chronic condition: a scoping review of qualitative research. Pharmaceutics. 2021 Jul 20;13(7):1100. PMID: 34371791. doi:10.3390/pharmaceutics13071100. Barillet M, Prevost V, Joly F, Clarisse B. Oral antineoplastic agents: how do we care about adherence? Br J Clin Pharmacol. 2015 Dec;80(6):1289–1302. doi:10.1111/bcp.12734. Arthurs G, Simpson J, Brown A, Kyaw O, Shyrier S, Concert CM. The effectiveness of therapeutic patient education on adherence to oral anti-cancer medicines in adult cancer patients in ambulatory care settings: a systematic review. JBI Database System Rev Implement Rep. 2015 Jun 12;13(5):244–92. doi:10.11124/jbisrir-2015-2057. Fitzmaurice C, Dicker D, Pain A, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease Study 2015. JAMA Oncol. 2017 Apr 1;3(4):524–48. doi:10.1001/jamaoncol.2016.5688. van Loggerenberg F, Gray D, Gengiah S, Kunene P, Gengiah TN, Naidoo K, et al. A qualitative study of patient motivation to adhere to combination antiretroviral therapy in South Africa. AIDS Patient Care STDS. 2015 May;29(5):299–306. doi:10.1089/apc.2014.0293. Srinivasan S, Kaur S, Chawla S, et al. Medication adherence in cancer patients: a comprehensive review. Cureus. 2024 Jan 22;16(1):e52721. doi:10.7759/cureus.52721. AlShehri W, Almotairi M, Alshakhs H, Orfali R. Medication adherence in palliative care patients. Cureus. 2022 May 25;14(5):e25322. doi:10.7759/cureus.25322. Knobel H, Alonso J, Casado JL, et al. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS. 2002 Mar 8;16(4):605–13. doi:10.1097/00002030-200203080-00012. Ortega Suárez FJ, Sánchez Plumed J, Pérez Valentín MA, Pereira Palomo P, Muñoz Cepeda MA, Lorenzo Aguiar D. Validación del cuestionario simplificado de adherencia a la medicación (SMAQ) en pacientes con trasplante renal en terapia con tacrolimus. Nefrología (Madr.) [Internet]. 2011 Nov-Dec [cited 2025 Aug 27];31(6):690-6. Available from: http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S0211-69952011000600011 Rodríguez Chamorro MA, García-Jiménez E, Amariles P, Rodríguez Chamorro A, Faus MJ. Revisión de tests de medición del cumplimiento terapéutico utilizados en la práctica clínica. Aten Primaria. 2008 Aug;40(8):413-8. PMID: 18755102. doi:10.1157/13125407. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 10 Nov, 2025 Reviewers invited by journal 30 Oct, 2025 Editor invited by journal 07 Oct, 2025 Editor assigned by journal 05 Oct, 2025 Submission checks completed at journal 05 Oct, 2025 First submitted to journal 05 Oct, 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7786354","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":542648365,"identity":"61c70cef-dafe-42f3-aa91-2625b8b799ef","order_by":0,"name":"Claudia Chávez Oyanadel","email":"","orcid":"","institution":"Centro de Investigación e Innovación del Cáncer. Fundación Arturo López Pérez Centro Oncológico OECI, Santiago de Chile","correspondingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"Chávez","lastName":"Oyanadel","suffix":""},{"id":542648366,"identity":"1f9004dc-5f4c-41be-91ae-c4a8735554f4","order_by":1,"name":"Macarena Manríquez-Mimica","email":"data:image/png;base64,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","orcid":"","institution":"Centro de Investigación e Innovación del Cáncer. Fundación Arturo López Pérez Centro Oncológico OECI, Santiago de Chile","correspondingAuthor":true,"prefix":"","firstName":"Macarena","middleName":"","lastName":"Manríquez-Mimica","suffix":""},{"id":542648367,"identity":"ba9e8c06-7323-4e4a-b4ba-5d318a3da3d8","order_by":2,"name":"Romina A. Vargas Aránguiz","email":"","orcid":"","institution":"Convenio Oncológico Fondo Solidario. Fundación Arturo López Pérez Centro Oncológico OECI, Santiago, Chile.","correspondingAuthor":false,"prefix":"","firstName":"Romina","middleName":"A. Vargas","lastName":"Aránguiz","suffix":""},{"id":542648369,"identity":"f405c844-9d20-43da-9156-1fad184f8921","order_by":3,"name":"Dorca E. Méndez Hernández","email":"","orcid":"","institution":"Convenio Oncológico Fondo Solidario. Fundación Arturo López Pérez Centro Oncológico OECI, Santiago, Chile.","correspondingAuthor":false,"prefix":"","firstName":"Dorca","middleName":"E. Méndez","lastName":"Hernández","suffix":""},{"id":542648370,"identity":"4052f4d0-925c-444e-bc0e-d680fbe058a4","order_by":4,"name":"María Hernandez-Carrera","email":"","orcid":"","institution":"Centro de Investigación e Innovación del Cáncer. Fundación Arturo López Pérez Centro Oncológico OECI, Santiago de Chile","correspondingAuthor":false,"prefix":"","firstName":"María","middleName":"","lastName":"Hernandez-Carrera","suffix":""}],"badges":[],"createdAt":"2025-10-05 18:38:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7786354/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7786354/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95663626,"identity":"e2b951aa-d675-4237-b45a-2bcd63994460","added_by":"auto","created_at":"2025-11-11 16:39:11","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81365,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/45022530d477b85038485850.docx"},{"id":95663687,"identity":"101793fe-d53a-4720-b14d-8232d55522ce","added_by":"auto","created_at":"2025-11-11 16:39:14","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":7732,"visible":true,"origin":"","legend":"","description":"","filename":"29eb3ac44fc9420f9481ed19680f2f77.json","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/e7b576f492986b8e25eb1641.json"},{"id":95663644,"identity":"ac12f3f8-c565-4252-85c0-4a2f0b0c77ce","added_by":"auto","created_at":"2025-11-11 16:39:12","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":68154,"visible":true,"origin":"","legend":"","description":"","filename":"29eb3ac44fc9420f9481ed19680f2f771enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/b793d5f0bc9e39bfedb52a9a.xml"},{"id":95663590,"identity":"8b699b5e-2953-4826-a0fe-fcb388f3524c","added_by":"auto","created_at":"2025-11-11 16:39:08","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":48742,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/45a62c1e208fa69fe569af4a.png"},{"id":95663533,"identity":"9f28ddc2-020a-4f39-84ec-073cdcdcfa3c","added_by":"auto","created_at":"2025-11-11 16:39:03","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":14259,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/d8ca97ff888ab222b1d9cda0.png"},{"id":95663691,"identity":"28daed7f-ef27-46c8-a87b-a712adeb9c23","added_by":"auto","created_at":"2025-11-11 16:39:14","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65421,"visible":true,"origin":"","legend":"","description":"","filename":"29eb3ac44fc9420f9481ed19680f2f771structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/017cec43119cf7f143e0f2be.xml"},{"id":95663665,"identity":"dec222a7-0a1b-460b-9443-8e254897c33a","added_by":"auto","created_at":"2025-11-11 16:39:13","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74291,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/a402a16cda0eccc7f05c9ca9.html"},{"id":95663523,"identity":"abdc30cf-92b0-4a04-86e2-a2dc06d0cd6c","added_by":"auto","created_at":"2025-11-11 16:39:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22581,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProgression-Free Survival Curve\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKaplan-Meier estimate of time to progression among study participants receiving High-Cost Oral Antineoplastic Drugs (HOCADs). The solid red line represents the survival function, and the shaded area indicates the 95% confidence interval.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/d766aaaa15a5626d1b681d68.png"},{"id":95797792,"identity":"89a4f96e-b88d-4ed5-81e5-04281c10d53a","added_by":"auto","created_at":"2025-11-13 08:10:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":595907,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7786354/v1/de1b0012-d8f1-4b2f-a32c-6df0ffa7391d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAdherence to High Cost Oral Antineoplastic Drugs in Oncological Patients of Arturo López Pérez Foundation Oncological Institute: An Observational Study\u003c/p\u003e","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eCancer represents a major public health problem worldwide, both in terms of magnitude and the burden of disease it entails, and incidence rates have continued to rise in most countries since 1990 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Advances in cancer treatment have been significant, particularly in recent years, becoming more specific, more personalized, and less invasive, which results in a better quality of life for patients. However, these improvements also require large investments and generate high personal, family, and state costs.\u003c/p\u003e\u003cp\u003eHigh-Cost Drugs (HCD) is a concept that may vary depending on the context in which it is used, but what all definitions have in common is that they demand an increasing volume of financial resources. In Chile, the most recent decree (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) established a national annual cost threshold for a high-cost treatment of 3.270 USD (Decree eighty-six, Law 20.850).\u003c/p\u003e\u003cp\u003eIn general, the administration of oral antineoplastic drugs (OAD) has accelerated in both curative and palliative settings. Therefore, the development of effective strategies to promote optimal adherence to cancer medication regimens has become a priority. The major advantages of OAD use are the level of independence and reduction of healthcare costs due to outpatient treatment (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Additionally, OAD offers benefits for patients such as greater convenience and less time away from home, which improves quality of life compared to intravenous treatment. However, adherence is more difficult to monitor, as are the adverse effects of the treatment (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere are several definitions regarding the meaning of \u0026ldquo;treatment adherence,\u0026rdquo; with no consensus on how it should be measured or approached. For the purposes of this study, we considered the World Health Organization (WHO) definition, which states that adherence is the extent to which a patient\u0026rsquo;s behavior in relation to medication intake corresponds with the agreed recommendations from a healthcare professional (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAmong the factors studied that impact positive treatment adherence are patients\u0026rsquo; knowledge about their diagnosis and treatment, as well as their perception of the medication as beneficial and necessary for their health (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). A key facilitator of medication adherence is patient motivation. If a patient is aware of the drug\u0026rsquo;s benefits and necessity, their motivation will increase. Support from friends, family, and co-workers also fosters medication adherence (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). On the contrary, non-adherence to treatment increases the disease burden and leads to negative consequences, resulting in higher treatment failure rates, greater hospitalization rates, and consequently higher healthcare costs (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA qualitative study in breast cancer patients observed that good communication and adequate information are the most critical factors in facilitating better treatment adherence (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Adequate therapeutic adherence has been shown to improve disease prognosis, in addition to strengthening appropriate control measures for allocating resources in prevention, diagnosis, treatment, palliative care, and monitoring effectiveness (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDespite the significant advances in therapeutic management and comprehensive treatment of oncological diseases, the current concern is the lack of treatment adherence. The main causes identified are drug-related adverse effects, the high costs involved, the complexity of therapeutic regimens, and the multiple food-drug and drug-drug interactions (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAccording to the literature, adherence rates to OAD vary widely depending on the population, cancer type, and measurement method (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). It is estimated that between 20% and 50% of patients do not adhere to prescribed treatment regimens, indicating that they \u0026ldquo;do not comply\u0026rdquo; or \u0026ldquo;do not adhere\u0026rdquo; to therapy (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e The Arturo L\u0026oacute;pez P\u0026eacute;rez Foundation Oncological Institute (FALP, by its acronym in Spanish), is a comprehensive cancer care center located in Santiago, Chile, which treats an average of 3,000 patients per year from across the country. In addition to providing highly complex oncological treatments, including surgery, radiotherapy, and systemic therapies.\u003c/p\u003e\u003cp\u003eFALP has a solidarity-based health financing system currently covering more than one million beneficiaries through a monthly contribution. This solidarity financing, called \u0026ldquo;Convenio Oncol\u0026oacute;gico\u0026rdquo; (Oncological Insurance, OI), covers the copayment of all services related to treatment and follow-up received at FALP for any type of cancer, with no coverage caps or event limits. There is also an HCD Committee, composed by a Health Technology Assessment Unit and specialists in the field, which evaluates potential beneficiaries for these medications.\u003c/p\u003e\u003cp\u003eMoreover, the OI population is highly diverse in terms of geographic distribution, age range, and oncological diagnosis; this is also reflected in the beneficiaries of HCOADs. However, we are unaware whether these variables influence or are associated with greater or lesser treatment adherence.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e The aim of this study was to estimate adherence to prescribed high-cost oral antineoplastic drugs among patients affiliated to the Arturo L\u0026oacute;pez P\u0026eacute;rez Foundation Oncological Institute, to describe their demographic and clinical characteristics, and to assess whether therapeutic adherence impacts progression-free survival.\u003c/p\u003e\u003cp\u003eAn observational, prospective study was conducted with a follow-up period of twelve months. This study was approved by the Scientific Ethics Committee of FALP, which is accredited in accordance with current local legislation (code No. 2020-037-QUA-SIN-INT). The target population consisted of OI affiliates over 18 years of age who received HCOADs financing for their oncological treatment during 2020\u0026ndash;2021. Data collection was performed using the Simplified Medication Adherence Questionnaire (SMAQ), adapted for use in cancer patients (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). This instrument has been validated in several countries (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) and has the advantage of being a brief, simple, cost-effective, and easy-to-administer method; however, it may overestimate adherence, presenting a low negative predictive value (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e\u003cp\u003ePatients meeting the selection criteria were contacted by phone and invited to participate in the study. Only those who expressed interest were sent an Informed Consent Form via email, explaining the study\u0026rsquo;s objectives and implications, and informing them about the confidentiality and voluntariness of their participation. The SMAQ questionnaire was administered by phone on a monthly basis (30\u0026thinsp;\u0026plusmn;\u0026thinsp;4 days). Participants were contacted by the same OI coordinator, who was previously trained in administering the instrument. The date of study entry was considered as the date of the first telephone interview. Patients were contacted until the end of follow-up, defined as 12 months post first interview, or disease progression as reported by a physician upon new findings, or withdrawal of consent, or death, whichever occurred first.\u003c/p\u003e\u003cp\u003eOther variables measured included demographic data (sex, age, insurance, and region), oncological diagnosis, type of HCOADs used, and drug-related toxicity, defined as a change in therapy by the treating physician due to a clinically significant adverse event or an event that incapacitated the patient for any other reason.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eAn exploratory analysis of the results was performed using tables and graphs. For categorical variables, proportions with their 95% confidence intervals were calculated, while quantitative data were expressed as medians and interquartile ranges (IQR, corresponds to the range between the 25th and 75th percentiles). To evaluate bivariate associations, the Student\u0026rsquo;s t-test and Kruskal-Wallis test were used for quantitative variables, and the chi-square test or Fisher\u0026rsquo;s exact test were used for categorical variables, depending on the nature of the data.\u003c/p\u003e\u003cp\u003eSurvival was calculated from the date of the first interview until the date of death or censoring, considering censoring for loss to follow-up due to progression or toxicity. The final status variable was used to define the states, in order to exclude from the survival curve those patients who died after the end of the study.\u003c/p\u003e\u003cp\u003eSurvival curves were estimated using the Kaplan-Meier method, and differences in survival between groups were assessed using the log-rank test. A p-value less than 0.05 was considered statistically significant. Statistical analyses were performed using R software version 4.4.2.\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eDuring the years 2020 and 2021, ninety-two patients were beneficiaries of HCOADs, 65.2% women (n\u0026thinsp;=\u0026thinsp;60) and 34.8% men (n\u0026thinsp;=\u0026thinsp;32), with a median age of 60.5 years (IQR 15.5 years). The most frequent oncological diagnoses were breast cancer, accounting for 33.7% (n\u0026thinsp;=\u0026thinsp;31), and lung cancer, with 28.3% (n\u0026thinsp;=\u0026thinsp;26) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic and clinical characteristics of HOCADs beneficiary patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePatients (%) (n)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34,8% (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65,2% (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMedian: 60,5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eIQR: 15,5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"7\"\u003e\n \u003cp\u003e\u003cstrong\u003eOncological diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBreast cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33,7% (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLung cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28,3% (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKidney cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15,2% (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematologic cancers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13,0% (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProstate cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,3% (n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOvarian cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,3% (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSkin cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,2% (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003eSummarizes the demographic (sex, age) and clinical (oncological diagnosis) characteristics of patients receiving High-Cost Oral Antineoplastic Drugs (HOCADs). Categorical variables are presented as percentages (n); continuous variables are reported as median and interquartile range (IQR). Abbreviations: HOCADs, High-Cost Oral Antineoplastic Drugs; IQR, Interquartile Range.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eOf these ninety-two patients, forty-nine (53.3%) agreed to participate in the study. The sex distribution showed that 69.4% (n\u0026thinsp;=\u0026thinsp;34) were women and 30.6% (n\u0026thinsp;=\u0026thinsp;15) were men, with a median age of 59 years (IQR 16 years). Patients mainly came from Region Metropolitana (30.6%, n\u0026thinsp;=\u0026thinsp;15), followed by Biob\u0026iacute;o (12.2%, n\u0026thinsp;=\u0026thinsp;6) and Valpara\u0026iacute;so (10.2%, n\u0026thinsp;=\u0026thinsp;5); only the regions of Ays\u0026eacute;n and Los R\u0026iacute;os had no cases. Regarding health insurance, 67.3% (n\u0026thinsp;=\u0026thinsp;33) were affiliated with private health insurance providers, while 32.7% (n\u0026thinsp;=\u0026thinsp;16) were affiliated with the public health insurance system.\u003c/p\u003e\n\u003cp\u003eThe most frequent diagnoses were breast cancer at 38.8% (n\u0026thinsp;=\u0026thinsp;19), lung cancer at 20.4% (n\u0026thinsp;=\u0026thinsp;10), and hematologic cancers combined at 14.3% (n\u0026thinsp;=\u0026thinsp;6). Regarding the drugs used, Ribociclib was the most common at 32.7% (n\u0026thinsp;=\u0026thinsp;16), followed by Everolimus at 12.2% (n\u0026thinsp;=\u0026thinsp;6), and Osimertinib and Afatinib each at 10.2% (n\u0026thinsp;=\u0026thinsp;5), which corresponded to the associated diagnoses (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographic and clinical characteristics of study participants\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePatients (%) (n)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30,6% (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69,4% (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMedian: 59 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eIQR: 16 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"16\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArica y Parinacota\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2% (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTarapac\u0026aacute;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2% (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntofagasta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2% (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtacama\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,1% (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCoquimbo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,1% (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eValpara\u0026iacute;so\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10,2% (n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMetropolitana\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30,6% (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eO\u0026rsquo;Higgins\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,1% (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaule\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,1% (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026Ntilde;uble\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,1% (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiob\u0026iacute;o\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12,2% (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLa Araucan\u0026iacute;a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,1% (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLos R\u0026iacute;os\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0% (n\u0026thinsp;=\u0026thinsp;0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLos Lagos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,1% (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAys\u0026eacute;n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0% (n\u0026thinsp;=\u0026thinsp;0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMagallanes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,1% (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003eSummarizes the demographic (sex, age, and region) characteristics of the study participants who were receiving High-Cost Oral Antineoplastic Drugs (HOCADs). Categorical variables are presented as percentages (n); continuous variables are reported as median and interquartile range (IQR). Regions correspond to first-level administrative divisions of Chile. Abbreviations: HOCADs, High-Cost Oral Antineoplastic Drugs; IQR, Interquartile Range.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIn terms of adherence, all participating patients remained in the study until the end of follow-up (100% adherence). However, various outcomes were observed during the study, including disease progression, toxicity, and death. Specifically, 36.7% (n\u0026thinsp;=\u0026thinsp;18) experienced disease progression, 4.1% (n\u0026thinsp;=\u0026thinsp;2) experienced toxicity, and 4.1% (n\u0026thinsp;=\u0026thinsp;2) died during follow-up.\u003c/p\u003e\n\u003cp\u003eThe median age of the patients who experienced progression was sixty-one years, while the median age of patients who remained on treatment until the end of follow-up was fifty-five years; however, this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.1327).\u003c/p\u003e\n\u003cp\u003eThe most represented diagnoses among patients with progression were breast cancer at 44.4% (n\u0026thinsp;=\u0026thinsp;8) and lung cancer at 22.2% (n\u0026thinsp;=\u0026thinsp;4). Deaths occurred in patients with prostate cancer (n\u0026thinsp;=\u0026thinsp;1) and kidney cancer (n\u0026thinsp;=\u0026thinsp;1). No statistically significant differences were found between diagnosis and final status at follow-up (p\u0026thinsp;=\u0026thinsp;0.6482).\u003c/p\u003e\n\u003cp\u003eThe most frequently used drugs in the progression group were Ribociclib at 38.9% (n\u0026thinsp;=\u0026thinsp;7), and Everolimus and Osimertinib at 16.7% each (n\u0026thinsp;=\u0026thinsp;3). In the treatment group, Ribociclib at 33.3% (n\u0026thinsp;=\u0026thinsp;9) and Dasatinib at 18.5% (n\u0026thinsp;=\u0026thinsp;5) were the most common drugs, while in the deceased patients group, Enzalutamide (n\u0026thinsp;=\u0026thinsp;1) and Sunitinib (n\u0026thinsp;=\u0026thinsp;1) were used. However, no significant differences were found between these variables (p\u0026thinsp;=\u0026thinsp;0.08496).\u003c/p\u003e\n\u003cp\u003eWhen calculating the 12-month progression-free survival, it was 0.5, meaning that the probability of these patients experiencing disease progression by month 12 was 50%. The survival curve shows that during the first seven months, the probability of progression is low and stable; however, after this period, the risk of progression increases and becomes more pronounced. This difference was statistically significant (p\u0026thinsp;=\u0026thinsp;0.00000) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn contrast to other studies (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), all patients adhered to the treatments prescribed by their treating physician during the follow-up period in this study. This finding can be attributed to several key factors. First, the financial coverage provided to patients for medication costs played a crucial role. Another relevant factor was the constant monthly communication with patients. This strategy allowed not only a continuous reminder regarding treatment adherence but also the opportunity to address questions related to symptoms associated with treatment use and other administrative matters. Patients reported that the regular calls helped them feel supported and valued, which could have contributed to the observed adherence. As highlighted in other studies (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), this reinforces the importance of communication in managing adherence.\u003c/p\u003e\u003cp\u003eRegarding toxicity, the results showed that the therapies administered did not cause serious or severe adverse effects, and only two patients in the cohort experienced side effects, but they continued adhering to the treatment. This may have contributed to fewer interruptions in their treatment, maintaining their adherence until the end of the study. This contrasts with findings in the literature (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), where toxicity is considered a significant risk factor for maintaining adherence.\u003c/p\u003e\u003cp\u003eDespite full adherence, disease progression occurred in 36.7% of patients during the study. These results suggest that therapeutic adherence may be relevant, but it is not necessarily a guarantee that the disease will not progress. This could be explained by other variables not measured in this study, such as disease stage, genetic load of the patients, and other comorbidities, which could be part of future research based on these findings.\u003c/p\u003e\u003cp\u003eOn the other hand, based on progression-free survival results, we noted that although the disease remained stable at the beginning of the treatment, by the seventh month, the risk of progression increased sharply, which underscores the importance of constant monitoring in these patients during treatment (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIt is important to note that adherence, toxicity, and progression are not completely pure variables, as HCOADs are generally administered in combination with other therapies, such as cytotoxic chemotherapy or radiotherapy. Therefore, the results should be interpreted with caution, as the influence of these other therapies may have affected the outcomes.\u003c/p\u003e\u003cp\u003eAnother point worth mentioning, although it was not the primary objective of this study, is that all patients expressed disappointment at the end of their follow-up in the study. Many thanked the calls, and some even asked if they could continue contacting the executive to resolve future questions, which highlights the value of a personalized and close approach in oncological treatment.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis study provides valuable insights from a real-world context regarding adherence to oncological medications. The findings suggest that a combination of financial support, continuous communication and an environment that values patients\u0026rsquo; needs can have a positive impact on treatment adherence. These results pave the way for further research on how to optimize support for oncology patients in clinical practice.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOAD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eoral antineoplastic drugs\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHCOADs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehigh-cost oral anticancer drugs\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePFS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eprogression-free survival\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eOncological Insurance\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSMAQ\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSimplified Medication Adherence Questionnaire\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHCD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHigh-Cost Drugs\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eWorld Health Organization\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFALP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eArturo L\u0026oacute;pez P\u0026eacute;rez Foundation Oncological Institute\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInterquartile ranges\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Scientific Ethics Committee of Fundación Arturo Benitez, which is accredited in accordance with current local legislation (code No. 2020-037-QUA-SIN-INT).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due to Chilean Law N° 19.628, the “Law on Protection of Private Life,” which regulates the processing of personal data and protects sensitive information, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: CCHO, MMM. Methodology: CCHO, MMM. Data curation: RVA, DMH. Formal Analysis: CCHO. Writing – Original Draft, Writing – Review \u0026amp; Editing, Visualization: CCHO, MMM, MHC. All authors gave final approval for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work benefited from the collaboration of the FALP´s solidarity-based health financing system “Convenio Oncológico” with special acknowledgment to Ms. Ingrid Wullfrodt, who provided continuous and compassionate support to the patients throughout the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFitzmaurice C, Dicker D, Pain A, et al. The global burden of cancer 2013. JAMA Oncol. 2015 Jul;1(4):505\u0026ndash;27. PMID: 26181261.\u003c/li\u003e\n\u003cli\u003eLibrary of the National Congress. Law No. 20.850: Establishes a Financial Protection System for High-Cost Diagnoses and Treatments [Internet]. Santiago: Library of the National Congress; [cited 2025 Aug 26]. Available from: https://www.bcn.cl/leychile/navegar?idNorma=1078148\u003c/li\u003e\n\u003cli\u003eRosenberg SM, Petrie KJ, Stanton AL, Ngo L, Finnerty E, Partridge AH, et al. Interventions to enhance adherence to oral antineoplastic agents: a scoping review. J Natl Cancer Inst. 2020 May 1;112(5):443-65. PMID: 31899790. doi:10.1093/jnci/djz244.\u003c/li\u003e\n\u003cli\u003eMueller-Sch\u0026ouml;ll A, Groenland SL, Scherf-Clavel O, van Dyk M, Huisinga W, Michelet R, et al. Therapeutic drug monitoring of oral targeted antineoplastic drugs. Eur J Clin Pharmacol. 2021 Apr;77(4):441\u0026ndash;64. PMID: 33165648. doi:10.1007/s00228-020-03014-8.\u003c/li\u003e\n\u003cli\u003eOlivera-Fern\u0026aacute;ndez R, Fern\u0026aacute;ndez-Ribeiro F, Pi\u0026ntilde;eiro-Corrales G, Crespo-Diz C. Adherencia al tratamiento antineopl\u0026aacute;sico oral. Farm Hosp. 2014 Nov 3;38(6):475-81. PMID: 25542658. doi:10.7399/fh.2014.38.6.8061.\u003c/li\u003e\n\u003cli\u003eSabat\u0026eacute; E, editor. Adherence to long-term therapies: Evidence for action [Internet]. Geneva: World Health Organization; 2003. 196 p. [cited 2025 Aug 26]. Available from: https://apps.who.int/iris/bitstream/handle/10665/42682/9241545992.pdf\u003c/li\u003e\n\u003cli\u003eKvarnstr\u0026ouml;m K, Westerholm A, Airaksinen M, Liira H. Factors contributing to medication adherence in patients with a chronic condition: a scoping review of qualitative research. Pharmaceutics. 2021 Jul 20;13(7):1100. PMID: 34371791. doi:10.3390/pharmaceutics13071100.\u003c/li\u003e\n\u003cli\u003eBarillet M, Prevost V, Joly F, Clarisse B. Oral antineoplastic agents: how do we care about adherence? Br J Clin Pharmacol. 2015 Dec;80(6):1289\u0026ndash;1302. doi:10.1111/bcp.12734.\u003c/li\u003e\n\u003cli\u003eArthurs G, Simpson J, Brown A, Kyaw O, Shyrier S, Concert CM. The effectiveness of therapeutic patient education on adherence to oral anti-cancer medicines in adult cancer patients in ambulatory care settings: a systematic review. JBI Database System Rev Implement Rep. 2015 Jun 12;13(5):244\u0026ndash;92. doi:10.11124/jbisrir-2015-2057.\u003c/li\u003e\n\u003cli\u003eFitzmaurice C, Dicker D, Pain A, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease Study 2015. JAMA Oncol. 2017 Apr 1;3(4):524\u0026ndash;48. doi:10.1001/jamaoncol.2016.5688.\u003c/li\u003e\n\u003cli\u003evan Loggerenberg F, Gray D, Gengiah S, Kunene P, Gengiah TN, Naidoo K, et al. A qualitative study of patient motivation to adhere to combination antiretroviral therapy in South Africa. AIDS Patient Care STDS. 2015 May;29(5):299\u0026ndash;306. doi:10.1089/apc.2014.0293.\u003c/li\u003e\n\u003cli\u003eSrinivasan S, Kaur S, Chawla S, et al. Medication adherence in cancer patients: a comprehensive review. Cureus. 2024 Jan 22;16(1):e52721. doi:10.7759/cureus.52721.\u003c/li\u003e\n\u003cli\u003eAlShehri W, Almotairi M, Alshakhs H, Orfali R. Medication adherence in palliative care patients. Cureus. 2022 May 25;14(5):e25322. doi:10.7759/cureus.25322.\u003c/li\u003e\n\u003cli\u003eKnobel H, Alonso J, Casado JL, et al. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS. 2002 Mar 8;16(4):605\u0026ndash;13. doi:10.1097/00002030-200203080-00012.\u003c/li\u003e\n\u003cli\u003eOrtega Su\u0026aacute;rez FJ, S\u0026aacute;nchez Plumed J, P\u0026eacute;rez Valent\u0026iacute;n MA, Pereira Palomo P, Mu\u0026ntilde;oz Cepeda MA, Lorenzo Aguiar D. Validaci\u0026oacute;n del cuestionario simplificado de adherencia a la medicaci\u0026oacute;n (SMAQ) en pacientes con trasplante renal en terapia con tacrolimus. Nefrolog\u0026iacute;a (Madr.) [Internet]. 2011 Nov-Dec [cited 2025 Aug 27];31(6):690-6. Available from: http://scielo.isciii.es/scielo.php?script=sci_arttext\u0026amp;pid=S0211-69952011000600011\u003c/li\u003e\n\u003cli\u003eRodr\u0026iacute;guez Chamorro MA, Garc\u0026iacute;a-Jim\u0026eacute;nez E, Amariles P, Rodr\u0026iacute;guez Chamorro A, Faus MJ. Revisi\u0026oacute;n de tests de medici\u0026oacute;n del cumplimiento terap\u0026eacute;utico utilizados en la pr\u0026aacute;ctica cl\u0026iacute;nica. Aten Primaria. 2008 Aug;40(8):413-8. PMID: 18755102. doi:10.1157/13125407. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Medication Adherence, Antineoplastic Agents, Cancer Treatment, Progression-Free Survival, Patient Support","lastPublishedDoi":"10.21203/rs.3.rs-7786354/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7786354/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e\u003cp\u003eCancer remains a major global public health challenge, with incidence and treatment costs steadily increasing. The use of oral antineoplastic drugs (OAD) has expanded due to their convenience and positive impact on patients\u0026rsquo; quality of life, but ensuring optimal adherence remains a critical issue. Non-adherence can compromise treatment effectiveness, increase healthcare costs, and worsen clinical outcomes. This study aimed to evaluate adherence to high-cost oral anticancer drugs (HCOADs) among oncological patients from Arturo L\u0026oacute;pez P\u0026eacute;rez Foundation Oncological Institute, and to explore its association with demographic and clinical characteristics as well as progression-free survival (PFS).\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e\u003cp\u003eA prospective observational study was designed with a 12-month follow-up period. Patients enrolled in the Oncological Insurance (OI) of Arturo L\u0026oacute;pez P\u0026eacute;rez Foundation Oncological Institute who received HCOADs between 2020 and 2021 were included. Adherence was assessed monthly through the telephone administration of the Simplified Medication Adherence Questionnaire (SMAQ). Demographic and clinical variables, as well as relevant clinical outcomes (disease progression, adverse events, and mortality), were collected. Descriptive and survival analyses (Kaplan\u0026ndash;Meier) were performed\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e\u003cp\u003eOut of ninety-two eligible patients, forty-nine participated in the study (53.3%). All participants maintained full adherence throughout the follow-up period. However, 36.7% experienced disease progression, 4.1% developed treatment-related toxicity, and 4.1% died. The 12-month PFS rate was 50%. A marked increase in progression was observed after the seventh month. No statistically significant associations were found between adherence and clinical outcomes.\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e\u003cp\u003eFull adherence may be influenced by financial support and personalized follow-up. Nevertheless, the observed disease progression suggests that adherence alone is not sufficient to ensure favorable outcomes. A comprehensive approach that incorporates additional clinical and social determinants is warranted.\u003c/p\u003e","manuscriptTitle":"Adherence to High Cost Oral Antineoplastic Drugs in Oncological Patients of Arturo López Pérez Foundation Oncological Institute: An Observational Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-11 16:34:07","doi":"10.21203/rs.3.rs-7786354/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"89998547376684847477772039761389464526","date":"2025-11-11T04:45:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-30T16:50:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-07T09:37:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-06T00:16:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-06T00:14:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-10-05T18:32:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"880c2ab8-8892-4f4c-b3c0-60ad7063c190","owner":[],"postedDate":"November 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-11T16:34:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-11 16:34:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7786354","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7786354","identity":"rs-7786354","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}