Encorafenib plus cetuximab in patients with metastatic, BRAF V600E-mutated, colorectal carcinoma: First effectiveness data of the European multi-centric, multi-national, non-interventional study—BERING-CRC.
Authors: Stintzing Sebastian , Virchow Isabel , Mueller-Huesmann Harald , von der Heyde Eyck , Bürkle Dieter , Stuebs Patrick , Wierecky Jan , Wein Axel , Gerger Armin , Köhler Martin , Arnold Dirk , Fritsch Ralph M , Vogel Arndt , Wagner Anna Dorothea , Winder Thomas , Koeberle Dieter , Prager Gerald W. , Kisro Jens 
Published: June 2024

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Background: Targeted treatment with encorafenib plus cetuximab (E+C) represents the standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer after prior systemic therapy. The approval was based on the data from the BEACON CRC trial; updated data of the trial showed a median progression free survival (mPFS) of 4.3 months and a median overall survival (mOS) of 9.3 months for the treatment with E+C compared to a mPFS of 1.5 months and a mOS of 5.9 months with chemotherapy plus cetuximab (hazard ratio [HR], 0.61 [95% CI, 0.48 to 0.77]) and an objective response rate (ORR) of 20% compared to 2%. The tolerability profile was consistent with the known safety profile of each agent and was generally well tolerated. As data from controlled clinical trials are based on a selected patient population, the non-interventional study (NIS) BERING CRC investigates the use of E+C at real-world conditions in a broader patient population. Methods: BERING CRC is an ongoing multi-national, multi-centric, prospective, longitudinal NIS. It represents the first NIS to investigate the real-world use of E+C in BRAF V600E-mutant metastatic colorectal cancer in Germany, Austria and Switzerland. The study aims to enroll 300 patients (pts) from 124 sites, treated according to the label. The primary study objective is to assess the 1-year OS rate. Secondary endpoints include effectiveness outcomes, quality of life, safety and tolerability of the treatment. The influence of prognostic factors on efficacy, as well as safety and tolerability will also be assessed. Results: Here we present the first planned effectiveness analysis based on the initial 100 enrolled pts (95 treated / 95 evaluable; median observation time: 5.9 mo). This analysis set showed an older patient population compared to the BEACON trial with a median age of 67 yrs (BEACON: 61 yrs) and fewer ECOG PS 0 patients (0/1/2/3: BERING 36/50/8/2 % vs BEACON 51/47/2/0 %). 96% presented with distant metastases (liver: 54%), with an involvement of ≥3 organ systems in 14%. E+C was mainly administered after one prior systemic therapy (73%). ORR was 24%, mPFS 5.3 months and mOS 10.3 months. Treatment emergent adverse events (TEAE) were reported in 73% of pts (grade 3/4: 38%). Main TEAE (≥10%, all grades) were: rash (12%) and nausea (11%). Conclusions: This first effectiveness analysis of BERING CRC shows the use of E+C in a real-world population. Despite the older study population and less ECOG PS 0 patients as compared to the pivotal study, the observed treatment effectiveness and safety profile are consistent with data from the BEACON CRC study. The recruitment of this study is ongoing and future analysis of the study will include an additional analysis of subgroups, effectiveness and QoL. Clinical trial information: NCT04673955 .