BRAF-mutant colorectal cancer: BRAF-directed therapy linked to the longest survival

Design

Reconstructed individual patient data meta-analysis of RCTs

Population

18 RCTs, 11,931 participants with BRAF-mutant metastatic colorectal cancer

Primary outcome

Overall and progression-free survival by targeted therapy class

Effect

First-line median OS 22.3 vs 17.1 vs 10.1 months; BRAF vs EGFR OS HR 0.43 (0.31–0.60)

This meta-analysis reconstructed individual patient data from published Kaplan–Meier curves in 18 randomised trials (11,931 participants) of targeted therapy in BRAF-mutant metastatic colorectal cancer.

In first-line studies, pooled median overall survival was 22.3 months with BRAF-directed regimens, 17.1 months with VEGF-targeted therapy and 10.1 months with EGFR-directed therapy without BRAF inhibition. BRAF-directed regimens were associated with better overall survival (HR 0.43) and progression-free survival (HR 0.47) than EGFR-directed therapy.

Comparisons across trials, even with reconstructed patient data, are vulnerable to differences in era, population and line of therapy. The message — test for BRAF V600E early and use a BRAF-directed regimen where available — fits current practice, but the size of the differences should not be taken literally.

• Test for BRAF V600E at diagnosis of metastatic colorectal cancer.
• Prefer a BRAF-directed regimen where available for BRAF V600E-mutant disease.
• Do not rely on EGFR-directed therapy without BRAF inhibition in BRAF-mutant disease.
• Check access and cost of BRAF inhibitors early, as availability varies.

Why it matters

BRAF status changes which targeted therapy gives patients the best chance.

Don't overread it

This compares results across different trials, which can exaggerate or distort differences between treatment classes.

The statistics, in plain English

An HR of 0.43 suggests a much lower death rate with BRAF-directed therapy than EGFR-directed therapy, but the comparison is indirect and adjusted only for study-level factors.

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