Abstract 374P
Background
BRAF-V600E mt in mCRC is more frequent among females. It’s already known sex and gender can impact on clinical activity and toxicity profile of several compounds including targeted therapy. However, this effect in mCRC treated with E-C+/-B still remains unclear. We analyzed the influence of sex in overall survival (OS), progression-free survival (PFS), and toxicity in this patient population.
Methods
Patients (pts) with mCRC candidates for E-C+/-B were included. Clinical data was collected prospectively. Clinical outcomes were calculated using survival Kaplan-Meier curves.
Results
From 2017 to 2021, 59 pts with mCRC were treated with E-C+/-B at our institution, 23 males (5 E/C/B, 18 E/C) and 36 women (15 E/C/B, 21 E/C). Overall, mOS and mPFS were 11.5 and 5.4 months, respectively. mOS in females was 12.52 vs 9.76 months in males (HR 1.21 95%CI 0.65-2.25 p 0.56). No significant differences were observed between men and women treated with the doublet (11.47 vs 11.53 months). Of note, women treated with the triplet showed a clear trend towards better mOS (20 vs 9 months, HR 3.22 95%CI 0.91-11.41 p 0.07) and mPFS (8.44 vs 5.72 months, HR 1.44 95%CI 0.49-4.24 p 0.5). Pts with G3-4 toxicities had significantly worse mOS (12.52 vs 6 months, 95%CI 1.52-10 p 0) and mPFS (5.62 vs 3.84 months 95%CI 1.13-6.60 p 0.03). Of note, G3-4 toxicities were more frequent in females (28% vs 17%). Globally women required higher dose modifications than males with both the doublet and the triplet (67% vs 60% and 71% vs 39%, respectively). When the doublet was used women had more arthralgias, pancreatitis, and cutaneous toxicity (any grade) being asthenia, liver, renal and cutaneous toxicity (any grade) more frequent with the triplet.
Conclusions
Among BRAF-V600E mt treated with E-C+/-B women seem to achieve greater clinical benefit particularly with the triplet combination but with an increased toxicity cost. These findings should be validated in a larger cohort considering not only sex but gender in order to better understand treatment modulation and improve outcomes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F.J. Ros Montana: Financial Interests, Institutional, Invited Speaker: Sanofi; Other, Other, Travel and accommodation expenses: Amgen, Pierre-Fabre, Merck, Sanofi. I. Baraibar Argota: Financial Interests, Personal, Invited Speaker: Sanofi. F. Salvà Ballabrera: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Sanofi, Merck, Servier, Roche. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daichii Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Avvinity, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb International Corporation, Genentech Inc, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, Pfizer, MedImmune, Menarini, Merus N V, Mirati; Non-Financial Interests, Invited Speaker, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Invited Speaker, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., Hutchinson Medipharma, HalioDX SAS, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array Biopharma, Sanofi, Bayer; Financial Interests, Institutional, Research Grant: Hoffman La-Roche, Sanofi Aventis, Amgen, Merck Serono, MSD, Boehringer Ingelheim, AbbVie, Pierre-Fabre, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Medimmune, Array Pharmaceuticals, AstraZeneca. All other authors have declared no conflicts of interest.