Stratifying survival benefit of encorafenib/cetuximab (EC) in BRAF V600E–mutant mCRC using clinical and inflammatory biomarkers: Real-world experience from greater Manchester.

Abstract

e15563 Background: BRAF V600E-mutant metastatic colorectal cancer (mCRC) is an aggressive subtype with historically poor outcomes. Although encorafenib/cetuximab (EC) improves survival, real-world data and the prognostic utility of clinical and inflammatory biomarkers remain limited. This study presents real-world data from a large UK cancer centre, incorporating expanded biomarker and prognostic group analyses. Methods: This retrospective cohort study included 100 adults with BRAF V600E-mutant mCRC receiving encorafenib/cetuximab (EC) between March 2020 and August 2025. Treatment continued until progression or unacceptable toxicity. Overall (OS) and progression-free survival (PFS) were estimated via Kaplan-Meier method. Prognostic groups (metastatic burden, liver involvement, time from metastatic diagnosis to EC) and baseline inflammatory indices (NLR, PLR, MLR, SIRI, PNI) were analysed using median cut-offs. Univariable and multivariable Cox models identified independent prognostic factors. Results: Among the 100 patients included (n = 100), 49% were females and the median age was 64 years. ECOG performance status was 1 in 78% of patients, and 68% presented with right-sided primary tumours. Liver metastases were observed in 59% of patients, and 45% had undergone prior primary tumour resection. Over a median follow-up of 10 months, the median PFS was 5.85 months (95% CI 5.27–6.42), and median OS was 10.25 months (95% CI 7.39–13.11). Patients with favourable prognostic characteristics (1 or 2 metastatic sites, no liver metastases, and time to initiation of EC from metastasis diagnosis more than 6 months) achieved significantly longer PFS (7.26 vs 5.42 months, p = 0.014) compared to those with poor characteristics. Low PLR was associated with improved PFS (6.24 vs 5.26 months, p = 0.05), while higher PNI independently predicted inferior PFS on multivariable analysis (HR 1.71, 95% CI 1.10–2.66, p = 0.02). For OS, a lower baseline NLR was linked to improved survival (13.8 vs 9.1 months, p = 0.03). No clinical biomarker was significant in multivariable analysis. Conclusions: In this large real-world cohort, encorafenib/cetuximab outcomes align with pivotal trial data. Composite clinical prognostic groups and simple inflammatory biomarkers (NLR, PNI) offer meaningful prognostic information, supporting improved risk stratification and personalized treatment in patients with BRAF V600E–mutant mCRC.