# Real-world outcomes of encorafenib, cetuximab ± binimetinib for BRAF‑mutated metastatic colorectal cancer: the BEETS (JACCRO CC‑18) study

## TL;DR

A study in Japan found that triplet therapy for BRAF-mutated colorectal cancer had similar survival outcomes to doublet therapy in real-world patients.

## Contribution

The study evaluates real-world effectiveness of triplet versus doublet therapy for BRAF-mutated metastatic colorectal cancer in Japan.

## Key findings

- Median OS was 12.9 months with no significant difference between triplet and doublet therapies.
- Among patients with poor prognostic factors, triplet therapy showed numerically better OS and PFS.
- Dose intensity of drugs was comparable between treatment groups.

## Abstract

Triplet therapy (encorafenib, cetuximab, and binimetinib) is recommended in Japan for BRAF V600E mutated metastatic colorectal cancer (mCRC) patients with poor prognostic factors (PFs) based on subgroup analyses of the BEACON CRC trial. We, therefore, conducted a nationwide prospective observational study to evaluate the real-world effectiveness of triplet versus doublet therapy (encorafenib plus cetuximab).

The BEETS trial (UMIN000045530) enrolled BRAF-mutated mCRC patients who received triplet or doublet as second- or third-line treatment. The primary endpoint was overall survival (OS). Exploratory analyses using inverse probability weighting (IPW) based on propensity scores were performed to adjust for poor PFs (ECOG performance status ≥1, ≥3 metastatic sites, elevated C-reactive protein, or unresected primary tumor).

In 203 enrolled patients, 195 patients were evaluable. Median age was 67 years; 52% were male. Dose intensity for encorafenib and cetuximab was comparable between the triplet and doublet cohorts. In the overall cohort, median OS and progression-free survival (PFS) were 12.9 and 4.9 months, respectively. After IPW adjustment, median OS was 14.0 months in the triplet cohort and 12.9 months in the doublet cohort (HR 0.87, 95%CI 0.57-1.33). Median PFS was 5.3 versus 4.2 months (HR 0.75, 95%CI 0.48-1.19). Among patients with at least one poor PF, both OS and PFS numerically favored the triplet regimen.

In real-world clinical practice, triplet and doublet therapies showed comparable survival outcomes, consistent with the BEACON trial. Triplet therapy may provide potential clinical benefit in patients with poor PFs.