Safety and efficacy of encorafenib–cetuximab combination in BRAFV600E-mutated metastatic colorectal cancer: real-world evidence from the CONFIDENCE Spanish multicenter study

Abstract

Background

Dual blockade therapy encorafenib–cetuximab (EC) was recently established as the standard of care for second- or third-line treatment for BRAF^V600E-mutated metastatic colorectal cancer (mCRC) patients based on BEACON phase III study results. The CONFIDENCE study aims to provide insight about the real-world (RW) safety and effectiveness of EC in a Spanish cohort.

Materials and methods

This retrospective study included BRAF^V600E-mutated mCRC patients treated in second line with EC in the RW setting. The primary endpoint (EC effectiveness) was measured by progression-free survival (PFS) and overall survival (OS). Key secondary endpoints were overall response rate (ORR), disease control rate (DCR), duration of response (DoR), potential factors affecting PFS and OS and safety.

Results

Eighty-one patients were included after at least 5 months of follow-up before study onset, 50.6% female with a median age of 66.1 years. Overall, 65% of patients debuted with synchronous metastatic disease. Patients received a median of six EC cycles. The median OS and PFS after 9.7 months of follow-up were 12.6 and 5.0 months, respectively. The median DoR was 5.8 months. ORR was 33.8% and DCR was 68.8%. Alkaline phosphatase, neutrophil/lymphocyte ratio and three or more metastatic lesions were accurate prognostic factors for OS. Additionally, the presence of liver metastases has prognostic value for PFS. The most reported adverse events (AEs) were skin-related toxicities (43.2%). Grade ≥3 AEs occurred in 13.5% of patients.

Conclusions

Our results align with the BEACON trial results, confirming the safety and efficacy of EC in the RW setting and additionally provide insight about survival prognostic factors.