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. 2023 Nov;149(14):12903-12912.
doi: 10.1007/s00432-023-05141-y. Epub 2023 Jul 19.

Impact of encorafenib on survival of patients with BRAFV600E-mutant metastatic colorectal cancer in a real-world setting

M Zurloh  1   2 , M Goetz  3 , T Herold  3   4   2 , J Treckmann  5   2 , P Markus  6 , B Schumacher  7 , D Albers  7 , A Rink  5   2 , V Rosery  1   2 , G Zaun  1   2 , K Kostbade  1   2 , M Pogorzelski  1   2 , S Ting  3   8 , H Schmidt  9   2 , R Stiens  1   2 , M Wiesweg  1   4   2 , M Schuler  1   4   2 , Stefan Kasper  10   11   12 , I Virchow  1   2
Affiliations

Impact of encorafenib on survival of patients with BRAFV600E-mutant metastatic colorectal cancer in a real-world setting

M Zurloh et al. J Cancer Res Clin Oncol. 2023 Nov.

Abstract

Purpose: Patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC) have a dismal prognosis. The best strategies in these patients remain elusive. Against this background, we report the clinical course of patients with BRAFV600E-mutant mCRC to retrieve the best treatment strategy.

Patients and methods: Clinico-pathological data were extracted from the electronic health records. Kaplan-Meier method was used to estimate overall (OS) and progression-free survival (PFS). Objective response rate (ORR) was assessed according to RECIST 1.1.

Results: In total, 51 patients were enrolled. FOLFOXIRI was administered to 12 patients; 29 patients received FOLFOX or FOLFIRI as first-line treatment. Median OS was 17.6 months. Median PFS with FOLFOXIRI (13.0 months) was significantly prolonged (HR 0.325) as compared to FOLFOX/FOLFIRI (4.3 months). However, this failed to translate into an OS benefit (p = 0.433). Interestingly, addition of a monoclonal antibody to chemotherapy associated with superior OS (HR 0.523). A total of 64.7% patients received further-line therapy, which included a BRAF inhibitor in 17 patients. Targeted therapy associated with very favourable OS (25.1 months).

Conclusion: Patients with BRAFV600E-mutated mCRC benefit from the addition of an antibody to first-line chemotherapy. Further-line treatment including a BRAF inhibitor has a dramatic impact on survival.

Keywords: BRAFV600E; Chemotherapy; Encorafenib; Metastatic colorectal cancer.

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Conflict of interest statement

Martin Schuler received honoraria as consultant (compensated) from Amgen, AstraZeneca, BIOCAD, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda, Honoraries for CME presentations from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis and Research funding to institution from AstraZeneca, Bristol Myers-Squibb Stefan Kasper received honoraria from Merck Serono, MSD, Novartis, BMS, Amgen, Roche, Sanofi-Aventis, Servier, Incyte, Pierre Fabre and Lilly; research funding from Merck Serono, Lilly, BMS, Roche. Isabel Virchow received travel support from Pierre Fabre. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

MS received honoraria as consultant (compensated) from Amgen, AstraZeneca, BIOCAD, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda, Honoraries for CME presentations from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis and Research funding to institution from AstraZeneca, Bristol Myers-Squibb. SK received honoraria from Merck Serono, MSD, Novartis, BMS, Amgen, Roche, Sanofi-Aventis, Servier, Incyte, Pierre Fabre and Lilly; research funding from Merck Serono, Lilly, BMS, Roche. IV received travel support from Pierre Fabre. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Funnel chart of palliative treatment regimen and conversion in first, second, third, fourth and fifth treatment line. FOLFOXIRI 5-fluorouracil, folinic acid, oxaliplatin, irinotecan, BRAFi BRAF inhibitor, BSC best supportive care
Fig. 2
Fig. 2
a Kaplan–Meier analysis for overall survival from start of palliative treatment. b Kaplan–Meier analysis for progression-free survival to first-line therapy
Fig. 3
Fig. 3
Forrest plot for odds ratios for overall response rate (ORR) and disease control rate (DCR) and hazard ratios for progression-free (PFS) and overall survival (OS) for patients which received a triplet chemotherapy in first line and a monoclonal antibody (mAbx), respectively
See this image and copyright information in PMC

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