Patterns of adjuvant endocrine therapy, discontinuations, toxicities and quality of life: Development of a model for early discontinuation using the CANTO cohort

Abstract Abstract. Long-term adherence to adjuvant endocrine therapy (ET, tamoxifen and aromatase inhibitors) is paramount for patients with early-stage breast cancer. Adherence to adjuvant endocrine therapy is hampered by numerous side effects associated with sustained estrogen deprivation. We aimed to describe recent real-world patterns of therapy, patients’ discontinuations of ET, toxicities, quality of life (QoL) and to develop a predictive model of early ET discontinuation. Methods. We used the first 9595 patients of the French CANTO cohort (NCT01993498), to evaluate among 6238 premenopausal and postmenopausal patients with HR+/HER2- stage I-III BC, who were prescribed adjuvant ET: a. treatment patterns of adjuvant ET including change of ET prescription during the follow-up course b. ET-associated toxicities and c. impact on QoL. Independent variables included medical history and toxicities as measured by : Common Toxicity Criteria Adverse Events (CTCAE) v4, Patient-Reported Outcomes (PROs) including European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ-C30) and Breast Cancer Module (BR23), and Hospital Anxiety and Depression Scale (HADS). Treatment discontinuation and treatment change were determined on the basis of patient’s declaration and medical decisions reported in the CANTO eCRF. We used patient data at 4 months from therapy initiation to train and evaluate on a held-out test set a machine-learning model (gradient-boosted trees) that is predictive of time to early discontinuation i.e. permanent discontinuation before four years of additional therapy. Results. 4052 post-menopausal patients and 2186 premenopausal patients were included in this analysis. Median follow-up after ET initiation is 3 years and 2 months. 86% of post-menopausal patients were prescribed a non-steroidal AI initially and 92% of premenopausal patients received tamoxifen first. Discontinuation rate of the first adjuvant endocrine therapy at 1 year was 14% and 10% in premenopausal and post-menopausal patients, respectively. Among 741 post-menopausal and 340 premenopausal patients who started a second ET, discontinuation of the second prescribed adjuvant ET at 1 additional year of therapy is 30% in both populations. Patients who switched from a first adjuvant ET to a second or further one continued to have more treatment-related toxicities and associated decrements in QoL. Exclusions due to data completeness and outcome definition led to 5331 patients being used for the model (4264 in the training set and 1067 in the validation set). In that population, the permanent discontinuation rate at 3 years is 6%. Our prediction model of time to early discontinuation obtains a C-index of 0.78 in the held-out validation set. Conclusion. Tolerability and continued adherence to ET remains a challenge for many patients. Early discontinuation models may assist in identifying patients who are likely to interrupt their adjuvant ET. Adapted clinical management, including robust support and management of toxicities, as well as new and more tolerable adjuvant endocrine therapies may improve the clinical outcomes of these patients. Citation Format: Felix Balazard, Aurélie Bertaut, Élise Bordet, Stéphane Mulard, Julie Blanc, Nathalie Briot, Gautier Paux, Asma Dhaini Merimeche, Olivier Rigal, Charles Coutant, Marion Fournier, Christelle Jouannaud, Patrick Soulie, Florence Lerebours, Paul-Henri Cottu, Olivier Tredan, Laurence Vanlemmens, Christelle Levy, Marie-Ange Mouret-Reynier, Mario Campone, Keri J. S. Brady, Medha Sasane, Megan Rice, Catherine Coulouvrat, Anne-Laure Martin, Alexandra Jacquet, Ines Vaz-Luis, Christina Herold, Barbara Pistilli. Patterns of adjuvant endocrine therapy, discontinuations, toxicities and quality of life: Development of a model for early discontinuation using the CANTO cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-08.