Abstract 96P
Background
We previously showed that men with BRAF-mutated melanoma had significantly lower benefit from targeted therapy as compared with women. Here we explored the hypothesis that such gender-based dimorphism in the efficacy of BRAF-pathway blockade extends to other tumor histotypes carrying pathogenic BRAF-mutations, such as colon cancer.
Methods
We retrospectively analyzed data from a cohort of patients with BRAF V600E-mutated, advanced colorectal-cancer (CRC), treated with anti-EGFR/BRAF/MEK targeted therapy. The primary objective was to assess the association between gender and outcome of patients treated with targeted therapy, in terms of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Multivariable Cox proportional hazard regression model was used to assess the association between gender and PFS and OS, adjusted for other relevant clinical, pathological and molecular prognostic factors, including ECOG PS (0 vs 1-2), primary tumor site (right-side vs left-side), microsatellite instability status (instable [MSI] vs stable [MSS]), number of metastatic sites at treatment start, treatment type (double targeted therapy [i.e., anti-EGFR + anti-BRAF] vs triple targeted therapy [i.e., anti-EGFR + anti-BRAF + anti-MEK]) and mutational status of the RNF43 gene (wild type versus mutated).
Results
Ninety-eight patients with advanced CRC were included in the analysis: 59 (60%) were women and 39 (40%) men. The ORR was 43.1% in women versus only 23.7% in men (p-value=0.05). Multivariable analysis adjusted for relevant clinical, pathological, and molecular variables associated with patients’ prognosis, showed a significantly shorter PFS and OS in men as compared with women: the adjusted-HR was, respectively, 1.65 (95%CI,1.00-2.69;p=0.04) for PFS and 1.83 (95%CI,1.08-3.08;p-value=0.02) for OS.
Conclusions
We confirmed a significant gender-based dimorphism in the efficacy of anti-EGFR/BRAF/MEK therapy in patients with advanced-CRC, that warrants further investigation.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Pala: Financial Interests, Institutional, Invited Speaker: Pierre Fabre. T.M. De Pas: Financial Interests, Institutional, Advisory Board: GSK, Boehringer Ingelheim; Financial Interests, Institutional, Sponsor/Funding: Pfizer, Blueprint Medicines, Gilead, Amgen, Merck. C.M. Catania: Financial Interests, Institutional, Other, travel support: AstraZeneca, Roche. G.L. Ceresoli: Financial Interests, Institutional, Advisory Role: Novocure, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Merck Sharp & Dohme, Bayer, Astellas. All other authors have declared no conflicts of interest.