- Design
- Systematic review and meta-analysis of 10 studies
- Population
- 1,478 patients with RAS wild-type mCRC on first-line anti-EGFR therapy
- Primary outcome
- PFS, OS and response by PIK3CA and BRAF status
- Effect
- PIK3CA OS HR 1.58 (1.22–2.05); BRAF PFS HR 1.68 (1.46–1.94)
A meta-analysis pooled 10 studies with 1,478 patients with RAS wild-type metastatic colorectal cancer treated with first-line anti-EGFR antibodies.
PIK3CA mutations were associated with shorter progression-free survival (HR 1.38) and overall survival (HR 1.58). BRAF mutations were associated with shorter progression-free (HR 1.68) and overall survival (HR 1.27). Response rates did not differ significantly.
BRAF testing is already standard before anti-EGFR therapy. The PIK3CA finding adds to evidence that RAS wild-type status alone does not guarantee benefit. These are prognostic associations, and the analysis cannot separate prognosis from a specific failure of anti-EGFR treatment.
The literature search ended in June 2019, so newer studies, including those of BRAF-targeted regimens, are not included.
- Test for BRAF, and consider PIK3CA, alongside extended RAS before first-line anti-EGFR therapy
- Use mutation status in discussing prognosis with RAS wild-type patients
- Note that the search ended in 2019 and predates newer BRAF-targeted regimens
Why it matters
RAS wild-type is not the whole story when choosing anti-EGFR therapy.
Don't overread it
Prognostic, not predictive: it does not show that mutation carriers should avoid anti-EGFR therapy.
The statistics, in plain English
An HR of 1.58 for overall survival with PIK3CA mutation means a death rate about 58% higher than in wild-type patients over the follow-up period.
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