Impact of Phosphatidylinositol 3-Kinase and B-Raf Mutations in Rat Sarcoma Wild-Type Metastatic Colorectal Cancer.
Wenjiang Wang, Tao Wang, Linfeng Qian et al.
✦ AI-curated · Sources linked
In 30 seconds
This systematic review and meta-analysis assessed whether PIK3CA and BRAF mutations were associated with outcomes among patients with RAS wild-type metastatic colorectal cancer receiving first-line EGFR inhibitor therapy. Ten studies including 1,478 patients were analysed. Both mutations were associated with worse progression-free and overall survival: for PIK3CA, the pooled hazard ratios were 1.38 for progression-free survival and 1.58 for overall survival; for BRAF, they were 1.68 and 1.27, respectively. Neither mutation was associated with a significant difference in objective response rate.
Key findings
- PIK3CA mutations were associated with worse progression-free survival (HR, 1.38; 95% CI, 1.11-1.71; p = 0.004) and overall survival (HR, 1.58; 95% CI, 1.22-2.05; p < 0.001).
- BRAF mutations were associated with worse progression-free survival (HR, 1.68; 95% CI, 1.46-1.94; p < 0.001) and overall survival (HR, 1.27; 95% CI, 1.09-1.49; p = 0.003).
- Objective response rate did not differ significantly by PIK3CA mutation status (RD, -0.12; 95% CI, -0.38 to 0.15; p = 0.38) or BRAF mutation status (RD, -0.12; 95% CI, -0.28 to 0.04; p = 0.15).
Why it matters
The findings distinguish survival outcomes from tumour response: mutation carriers had poorer progression-free and overall survival, while objective response rates were not significantly different. This may help frame interpretation of outcomes in RAS wild-type metastatic colorectal cancer treated with first-line EGFR inhibitors and highlights the potential relevance of molecular status to prognosis.
What to keep in mind
The authors state that prospective validation in larger studies is warranted; the pooled findings are based on 10 included studies.