Abstract P5-06-17: Post hot analysis of EORTC trial: Comedication and its impact on pCR rate
Authors: Grandal Beatriz , Ferrer Loic , Sella Nadir , Laas Enora , Poncet Coralie , Bonnefoi Herve , Latouche Aurelien , Brain Etienne , Reyal Fabien , Hamy Anne-Sophie 
Published: March 2020

Abstract
Context: Breast cancer increases with age, as does the incidence of chronic diseases and medications. There is a growing interest in chronically used medications that may influence the risk of cancer, as well as its progression. However, few studies focus on the influence of comedications on the outcomes of breast cancer (BC) and treatment. In addition, very little evidence is available regarding the impact of comedications on response to treatment in the neoadjuvant setting. Objectives: To assess whether the use of comedications modifies the response to chemotherapy. Methods: We reanalyzed the data from the EORTC 10994/BIG 1-00 phase III trial while focusing on chronic comedications prospectively registered. In this multicenter open-label trial (NCT00017095), 1856 patients with invasive breast cancer were stratified and randomly assigned to receive either a standard anthracycline regimen (FEC) or a taxane-based regimen (T-ET). Response to chemotherapy was assessed by pathological complete response (pCR) rates. We analyzed comedication according to level 1 of the Anatomical Therapeutic Chemical Classification System (ATC), grouping drugs by organ or system on which they act. A chronic comedication was defined by a comedication declared at inclusion and at least twice during follow-up visits. To estimate the average causal effect of comedication on pCR, we employed Inverse Probability Weighting (IPW) and standardization approaches, and we considered the Super Learner strategy to pick the best regression model from a list of candidates. Results: Out of 1856 patients included in the study, 1594 were included in this substudy (arm FEC n=839 (49.7%), arm T-ET, n=848 (50.3%)). The median age at inclusion was 48.5-year. BC subtypes were as follows: luminal BCs (40%), HER2-positive (25%), and TNBCs (14%). Overall, 11.4% of the patients (n=182) had at least one chronic comedication. The repartition of the comedications, according to the 1st level of the classification of the ATC, was as follows: Alimentary tract and metabolism (A): 2.6% (n=42), Cardiovascular system (C): 2% (n=32) and Nervous system (N): 6.6% (n=106). Patients taking drugs targeting cardiovascular system tend to be older with higher BMI and presented more frequently histological grade 3 and tumour status T4. The effect of comedications on pCR rates was different according to the chemotherapy regimen. The use of psychotropics (class N) in the T-ET arm was associated with increased pCR rates (OR = 2,3; 95% CI, 1.6 to 3,5; P =0.04), whereas this finding was not observed in the FEC arm (Pinteraction=0.04). Similarly, drugs targeting the alimentary system were associated with increased pCR rates in the FEC arm (OR = 11,4; 95% CI, 1,45 to 47; P = 0.03) whereas a lower pCR rate was observed in the T-ET arm (OR = 0,2; 95% CI, 0.1 to 0,8; P =0.02). Discussion: In this post hot analysis of EORTC trial, the use of different chronic comedication during neoadjuvant chemotherapy was associated with changes in pCR rates differentially according to the chemotherapy arm. This finding prompts for further research on the interactions between chemotherapy and chronic non-anti-cancer drugs use, to decipher if subgroups of patients may derive different benefits of harms from specific associations.
Citation Format: Beatriz Grandal, Loic Ferrer, Nadir Sella, Enora Laas, Coralie Poncet, Herve Bonnefoi, Aurelien Latouche, Etienne Brain, Fabien Reyal, Anne-Sophie Hamy. Post hot analysis of EORTC trial: Comedication and its impact on pCR rate [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-17.