Sequencing of Encorafenib Plus Cetuximab Among Patients With BRAF-Mutant Metastatic Colorectal Cancer

Post Hoc Analysis of the Phase 3 BEACON Trial 

At the 2023 World Congress on Gastrointestinal Cancers in Barcelona, Spain, Josep Tabernero, MD, PhD, shared data from a post-hoc analysis of the phase 3 BEACON trial which compared several factors between patients with BRAF V600E-mutant metastatic colorectal cancer treated with encorafenib plus cetuximab in the second-line setting compared to those treated in the third-line setting.

Although there were no major differences in clinical characteristics, outcomes, or the safety profile of patients in the BEACON trial who were treated in the second-line setting vs the third-line setting, Dr Tabernero concluded, “we tend to recommend that patients with BRAF-V600E mutant colorectal cancer are treated in the second-line setting as per the label of the indication of the combination of encorafenib-cetuximab.”

Transcript:

Hello, my name is Josep Tabernero. I'm a medical oncologist based in Barcelona, and the head of the medical oncology department at the Vall d'Hebron University Hospital. I'm here today to present on behalf of the investigators of the BEACON study, a post hoc analysis that we have performed to evaluate, according to the baseline characteristics of the patients, whether patients with BRAF-V600E mutated colorectal cancer have differences in the outcome depending on whether they were treated in the second-line setting, or in the third-line setting. 

For that, we collected all the clinical characteristics of the patients, including gender, age, concomitant morbidities, ECOG performance status, but also importantly, some characteristics of the tumor, like the location, whether the primary tumor was present or not, and the number of different organs with metastases. We evaluated both efficacy parameters like progression-free survival, overall survival, but also adverse events related to the experimental treatments, and compared to the control arm. 

Just to remind you, In this study, the population of patients included those with metastatic colorectal cancer, BRAF-V600E-mutated patients, who were treated in 2 experimental arms. One arm was with a triple combination of encorafenib, binimetinib, and cetuximab, what we call the triplet. The second one was the doublet combination of encorafenib, the BRAF inhibitor, and cetuximab, the EGFR inhibitor. And in the control arm, patients were treated either with irinotecan-cetuximab or FOLFIRI-cetuximab.

In analyzing the potential differences that patients could have on whether they were treated in the second-line setting or in the third-line setting, we didn't find any major difference, and it is balanced in the clinical characteristics of the patients. Moreover, we also look at the potential different toxicity profile that the patients could have if they were treated in the second-line or in the third-line. Likewise, we didn't find major differences in the safety profile of the patients if they were treated in the second-line or in the third-line. Finally, we look at the potential differential factors, for example, the therapies that patients could have received once they progress under the BEACON study. In the same way, we don’t find any major differences. 

Something that is important, however, is to realize that patients with metastatic colorectal cancer and the BRAF-V600E mutation, are patients that have a poor prognosis. These patients progress usually very rapidly. This means that more patients can be treated in the second-line than in the third-line. And this is very important because we want to offer these patients the best opportunities in terms of therapeutic options. This again reminds us how important is to test for the BRAF-V600E mutation upfront when patients are diagnosed first of advanced disease.

Although we didn't observe major differences in the clinical characteristics, the outcome, as well as the safety profile of patients in the BEACON study that were treated in the second-line setting or in the third-line setting, we tend to recommend that patients with BRAF-V600E mutant colorectal cancer are treated in the second-line setting as per the label of the indication of the combination of encorafenib-cetuximab. Thank you very much for your attention.

Source:

Tabernero J, Van Cutsem E, Yoshino T, et al. Clinical characteristics, efficacy, and safety in patients receiving second- or third-line encorafenib plus cetuximab (E+C) vs control for metastatic colorectal cancer (mCRC): BEACON CRC post hoc analysis. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-29