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. 2024 Jul;131(1):110-116.
doi: 10.1038/s41416-024-02711-w. Epub 2024 May 20.

Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab

Koen Zwart  1 , Sietske C M W van Nassau  1 , Frederieke H van der Baan  1   2 , Miriam Koopman  1 , Petur Snaebjornsson  3 , Anna J van Gestel  4 , Geraldine R Vink  1   4 , Jeanine M L Roodhart  5
Affiliations

Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab

Koen Zwart et al. Br J Cancer. 2024 Jul.

Abstract

Background: Encorafenib-cetuximab has been approved for pretreated BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients based on efficacy demonstrated in the randomized phase III BEACON trial. The aim of this real-world effectiveness study is to improve knowledge on the generalizability of trial results.

Methods: This population-based real-world study includes all mCRC patients in the Netherlands treated with encorafenib-cetuximab since approval. Individual patient data and pathology reports were collected. Overall survival (OS) was compared to BEACON and subgroup analyses were conducted for patients who would have been eligible and ineligible for BEACON.

Results: 166 patients were included with a median follow-up time of 14.5 months. Median OS was 6.7 months (95% CI:6.0-8.3) and differed from BEACON (9.3 months; 95% CI:8.0-11.3, p-value 0.002). Thirty-six percent of real-world patients would have been ineligible for the BEACON trial. Trial ineligible subgroups with symptomatic brain metastases and WHO performance status ≥2 had the poorest median OS of 5.0 months (95% CI:4.0-NR) and 3.9 months (95% CI:2.4-NR).

Conclusion: This real-world cohort of mCRC patients treated with encorafenib-cetuximab showed a clinically relevant efficacy-effectiveness gap for OS. The chance of survival benefit from encorafenib-cetuximab in patients with brain metastases and/or WHO performance status ≥2 is negligible as neither efficacy nor effectiveness has been demonstrated.

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Conflict of interest statement

KZ: Received research funding via institution from Bristol-Myers Squibb. SN: Received research funding via institution from Pierre-Fabre. Had travel, accommodations, or other expenses paid or reimbursed via institution by Servier. FB: Received research funding via institution from Bristol-Myers Squibb. MK: Received research funding via institution from Bayer, Bristol-Myers Squibb, Merck-Serono, Pierre Fabre, Servier, Roche, Sanofi, and Personal Genome Diagnostics. PS: Consulting or advisory role for Bayer, Bristol-Myers Squibb, MEDtalks via institution. AG: No competing interests. GV: Consulting or advisory role for Merck via institution. Received research funding via institution from Merck, Bayer, Personal Genome Diagnostics, Delphi Diagnostics, Bristol-Myers Squibb, Sirtex Medical. JR: Consulting or advisory role for Bayer, Bristol-Myers Squibb, Merck-Serono, Pierre Fabre, Servier via institution. Received research funding via institution from Bayer, Bristol-Myers Squibb, Merck-Serono, Pierre Fabre, Servier, HUB 4 organoids, and Cleara Biotech. Had travel, accommodations, or other expenses paid or reimbursed via institution by Servier.

Figures

Fig. 1
Fig. 1. Kaplan–Meier estimates of the overall survival of mCRC patients treated with encorafenib-cetuximab.
Patients treated in the BEACON trial versus the real-world cohort (a, b) and stratified by brain metastases and WHO performance status in the real-world cohort (c, d).
See this image and copyright information in PMC

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