625P - Efficacy and safety of the combination of encorafenib and cetuximab in patients with BRAF V600E mutated metastatic colorectal cancer: An AGEO real-world multicentre study

Background

The combination of encorafenib with cetuximab has become the standard of care in patients with BRAF V600E mutated metastatic colorectal cancer (mCRC), after a prior systemic therapy. This retrospective study aims to describe the efficacy and safety of encorafenib with cetuximab combination in the real-world setting.

Methods

All consecutive patients with BRAF V600E-mutated mCRC who received the combination encorafenib + cetuximab +/- binimetinib (e/c+/-b) from January 2020 to June 2022 in 24 French centers and 8 non-French centers were included.

Results

Overall, 201 patients were included, with 55% of women, a median age of 62 years and an ECOG-PS ≥2 in 20% of cases. Other main patients’ tumor characteristics were 60% of right-sided primary tumor, 11% of MSI/dMMR phenotype and liver and peritoneum being the 2 main metastatic sites (57% and 51%). The e/c+/-b combination was prescribed in 1^st line (L1) for 8 patients (4%), in 2^nd line (L2) for 113 patients (56%), in 3^rd line (L3) for 58 patients (29%), beyond L3 for 22 patients (11.3% ), with an addition of binimetinib for 21 patients (10%). With e/c treatment, 21% of patients experienced grade ≥3 adverse events (AEs), with each type of grade ≥3 AE observed in less than 5% of patients The most frequent grade 1-2 AEs were acneiform dermatitis/rash (43%), dry skin (29%), arthralgia (21%), and anemia (22%). The objective response rate under e/c+/-b was 32% and the disease control rate was 71%, all lines combined. Median PFS under e/c+/-b was 4.4 months (95% CI 3.9-5.6) and median OS was 9.1 months (95% CI 7.8-10.8). In multivariate analysis, the factors associated with a shorter PFS under e/c+/-b were the presence of liver metastases (HR: 1.6, p=0.02) and ECOG-PS≥2 (HR: 1.9, p=0.002) but not the line of treatment.

Conclusions

This real-world study showed that in patients with BRAF V600E mutated mCRC treated with encorafenib + cetuximab +/- binimetinib, efficacy data are very similar to those reported in the BEACON CRC registration trial. In this series, the main prognostic factors for this treatment are ECOG-PS≥2 and liver metastases. The safety profile was favorable with only 21% of patients experiencing a grade 3 or more AE.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

AGEO.

Funding

Pierre Fabre.

Disclosure

C. Gallois: Financial Interests, Personal, Advisory Board: Merck, Servier, Pierre Fabre, Sanofi. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: Organon, Novartis; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd, Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune; Non-Financial Interests, , Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Other, Travel, accommodations, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. S. Pernot: Financial Interests, Personal, Invited Speaker: Amgen, Bayer, Pierre Fabre; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, MSD, Servier. Y. Touchefeu: Financial Interests, Personal, Advisory Board: Pierre Fabre, Merck Serono. A. Turpin: Financial Interests, Personal, Expert Testimony: Merck Serono, Viatris, Incyte Biosciences; Financial Interests, Personal, Advisory Board: Servier, AstraZeneca, MSD, Bristol Myers Squibb. T. Mazard: Financial Interests, Personal, Advisory Board: Pierre Fabre, Pierre Fabre, Servier, AAA; Financial Interests, Personal, Invited Speaker: Servier, Sanofi; Financial Interests, Personal, Other, Development of clinical cases for regional meetings: Merck Serono; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Other, development of guidelines about molecular testing in colorectal cancers: INCA; Other, travel grant: Pierre Fabre, Merck Serono, Sanofi. P. Artru: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Roche, Servier, Pierre Fabre, Bristol Myers Squibb, Merck Serono; Financial Interests, Personal, Invited Speaker: Amgen. S. Stintzing: Financial Interests, Personal, Advisory Board: Amgen, Bayer, Lilly, Pierre Fabre, Merck KgaA, MSD, Roche, Sanofi, Taiho, Takeda; Financial Interests, Personal, Invited Speaker: Leo Pharma, AstraZeneca; Financial Interests, Institutional, Research Grant: Merck KGaA, Pierre Fabre, Roche. O. Dubreuil: Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: Sanofi, Pierre Fabre, Servier, MSD, AstraZeneca. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, Bristol Myers Squibb, Bayer; Non-Financial Interests, Member of Board of Directors: Federation Francophone de Cancerologie Digestive. J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Astellas, Merck, Servier, Pierre Fabre, Amgen, Bristol Myers Squibb, Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Merck, MSD, Novartis; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD). All other authors have declared no conflicts of interest.