Abstract 699: PIK3CA/BRAF mutations negatively affect outcome of patients with KRAS wild-type metastatic colorectal cancer treated with front line anti-EGFR monoclonal antibodies: Meta-analysis results

Abstract

Abstract BACKGROUND:The aim of this meta-analysis is to evaluate the effect of PIK3CA and BRAF mutations in patients with KRAS wild-type metastatic colorectal cancer receiving an EGFR monoclonal antibody (anti-EGFR) inhibitor in the first line therapy. METHODS:literature search was performed to identify studies exploring the association between PIK3CA/BRAF mutations and clinical outcomes of KRAS wild mCRC patients treated with anti-EGFR as a first line therapy. The primary clinical outcome is response rate (RR). The secondary outcomes include progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed effect model or random effect model according to heterogeneity between studies. RESULTS:Ten studies with 1,470 mCRC patients (357 for PI3K studies and 1,113 from BRAF studies) met selection criteria. We observed a trend towards lower RR in patients with PIK3CA mutations (2 studies, 137 patients; RR = 14.3% versus 52.4%; 95% confidence interval (CI) -0.12-0.02; P = 0.13). Patients with mutant-type PI3K have significant shorter PFS (3.8 vs 4.15 mos, HR = 1.36; 95% CI 1.04-1.77; P = 0.02), and OS (14.17 Vs 16.3 mos., HR = 1.50; 95% CI 1.14-1.97; P = 0.004) compared to those with wild PI3K. For BRAF, patients with mutant type have significant lower RR [4 studies, 416 patients; RR = 33% versus 39%; 95% confidence interval (CI) -0.16- 0.01; P = 0.03], shorter PFS (6 studies, 893 pts., 3.9 Vs 5.7 mos., HR = 1.72; 95% CI 1.47- 2.01; P = 0.00001), and shorter OS (6 studies, 1065 pts., 9.1 Vs 18.9 mos., HR = 1.22; 95% CI 1.04-1.44; P = 0.01) compared to those with wild type. CONCLUSION:These analyses suggest that patients with colorectal cancer and either PIK3CA or BRAF mutation have worse outcome when treated with anti-EGFR in the first line. Given their worse outcome, trials evaluating novel agents are needed in this group of patients. Meta-analyses on BRAFF and PIK3CA mutations in KRAS wild mCRCBRAF WildBRAF MutantHR (95% CI)p-valuePI3K WildPI3K MutantHR (95% CI)p-valueRR (%)39%33%-0.16 - 0.010.0352.4%14.3%-0.12 - 0.020.13PFS (mos)5.73.91.47 - 2.010.000014.153.81.04 - 1.770.02OS (mos)18.99.11.04 - 1.440.0116.314.71.14 - 1.970.004 Citation Format: Amr Mohamed, Kelly Schrapp, Taraq Attumi, Nabil F. Saba, Bassel F. El-Rayes. PIK3CA/BRAF mutations negatively affect outcome of patients with KRAS wild-type metastatic colorectal cancer treated with front line anti-EGFR monoclonal antibodies: Meta-analysis results. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 699. doi:10.1158/1538-7445.AM2015-699