PIK3CA Mutation Predictive of Relapse-Free Survival Benefit of Aspirin in Colorectal Cancer
Although nonsteroidal anti-inflammatory drugs such as aspirin have been shown to be protective against colorectal cancer and are associated with reduced disease recurrence and improved outcome, they are also associated with toxicities that limit their use in therapy. Recent data suggest that the benefit of aspirin in colorectal cancer may be limited to PIK3CA-mutant disease. In a study reported in Journal of Clinical Oncology, Enric Domingo, PhD, of The Wellcome Trust Centre for Human Genetics at the University of Oxford, and colleagues assessed the predictive performance of PIK3CA mutations for benefits from cyclooxygenase-2 inhibition with rofecoxib (Vioxx) and from low-dose aspirin. Presence of PIK3CA mutations did not predict relapse-free survival or overall survival benefits with rofecoxib treatment but did predict improved relapse-free survival among aspirin users.
Study Details
The study involved molecular analysis of tumors from 896 participants in the VICTOR trial, which compared rofecoxib with placebo after primary colorectal cancer resection. Relapse-free and overall survival were compared between rofecoxib and placebo recipients and between users and nonusers of low-dose aspirin according to PIK3CA mutation status.
Among all patients, 104 (12%) had PIK3CA mutations and 125 (14%) were regular users of low-dose aspirin (< 100 mg/d). Patients with PIK3CA mutations were significantly more likely to have KRAS mutations but not COX-2 overexpression. PIK3CA mutations were present in 50 of 445 placebo patients and 54 of 451 rofecoxib patients. Among patients without PIK3CA mutations, 681 were aspirin nonusers and 111 were aspirin users; among those with mutations, 90 were nonusers and 14 were users. Aspirin users were significantly older than nonusers and less likely to have received radiotherapy. Rofecoxib and placebo were received by similar proportions of aspirin users and nonusers with or without PIK3CA mutations.
No Survival Benefit of Rofecoxib in PIK3CA-Mutant Disease
After median follow-up of 61.5 months, 3-year relapse-free survival in rofecoxib vs placebo patients was 79.6% vs 80.0% among those with PIK3CA mutation (multivariate adjusted hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 0.50–2.98; P = .473 for interaction) and 86.4% vs 80.3% (adjusted HR = 0.85, 95% CI = 0.62–1.15) among those without mutations. Three-year overall survival was 92.6% vs 88.0% (adjusted HR = 2.39, 95% CI = 0.77–7.45; P = .298 for interaction) among those with PIK3CA mutations and 91.9% vs 91.9% (adjusted HR = 0.91, 95% CI = 0.63–1.32) among those without mutations.
Relapse-Free Survival Benefit With Aspirin
Three-year relapse-free survival for aspirin users vs nonusers was 100% vs 76.7% (adjusted HR = 0.11, 95% CI = 0.001–0.832; P = .024 for interaction) among those with PIK3CA mutations and 86.5% vs 82.8% (adjusted HR = 0.94, 95% CI = 0.59–1.49) among those without mutations. Three-year overall survival was 100% vs 88.9% (adjusted HR = 0.29, 95% CI = 0.04–2.33; P = .260 for interaction) among those with PIK3CA mutations and 91.9% vs 91.9% (adjusted HR = 0.95, 95% CI = 0.56–1.61) among those without mutations.
The investigators concluded, “Although tumor PIK3CA mutation does not predict benefit from rofecoxib treatment, it merits further evaluation as a predictive biomarker for aspirin therapy. Our findings are concordant with recent data and support the prospective investigation of adjuvant aspirin in PIK3CA-mutant [colorectal cancer].”
David N. Church, MBChB, DPhil, of the University of Oxford is the corresponding author for the Journal of Clinical Oncology article.
The VICTOR trial was supported by the University of Oxford and an educational study grant from Merck. The Wellcome Trust Centre for Human Genetics receives core funding from the Wellcome Trust.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
