PIK3CA Mutation Fails to Predict Outcome of Irinotecan-Based Therapy in Stage III Colon Cancer
In a study reported in Journal of the National Cancer Institute, Shuji Ogino, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, and colleagues from the Alliance for Clinical Trials in Oncology evaluated the association of PIK3CA mutations with outcome in patients with stage III colon cancer receiving adjuvant chemotherapy with either fluorouracil (5-FU) and leucovorin or irinotecan plus 5-FU/leucovorin. They found no association of PIK3CA mutation and outcome in this setting.
Study Details
The study examined the association of exon 9 and 20 PIK3CA mutations detected by polymerase chain reaction and pyrosequencing with recurrence-free, disease-free, and overall survival in 627 patients with stage III colon cancer receiving adjuvant 5-FU/leucovorin or irinotecan plus 5-FU/leucovorin in the Cancer and Leukemia Group B 89803 trial (Alliance). A Cox proportional hazards model was used to assess predictive ability of PIK3CA mutation with adjustment for clinical features and standard molecular pathology features including KRAS and BRAF mutations and microsatellite instability.
No Significant Associations
Overall, 88.2% of patients had wild-type PIK3CA and 11.8% had PIK3CA mutations, including 7.7% with exon 20 and 4.0% with exon 9 mutations. Of patients with wild-type PIK3CA, 51% received 5-FU/leucovorin; of those with mutations, 50% received 5-FU/leucovorin.
On multivariate analysis, there was no significant difference between the wild-type group and patients with any PIK3CA mutations (hazard ratio [HR] = 0.84, 95% confidence interval [CI] = 0.54–1.29), exon 9 mutations (HR = 0.88, 95% CI = 0.53–1.46), or exon 20 mutations (HR = 0.76, 95% CI = 0.36–163) in recurrence-free survival, disease-free survival (HR = 0.92, 95% CI = 0.62–1.35; HR = 0.91, 95% CI = 0.57–1.46; and HR = 0.94, 95% CI = 0.50–1.78, respectively), or overall survival (HR = 0.95, 95% CI = 0.63–1.45; HR = 0.98, 95% CI = 0.59–1.62; and HR = 0.90, 95% CI = 0.44–1.84, respectively) (all P > .40).
There were no significant difference in recurrence-free survival, progression-free survival, or overall survival for wild-type vs mutant groups in subgroups of patients with KRAS wild-type/BRAF wild-type, KRAS mutant/BRAF wild-type, or KRAS wild-type/BRAF mutant disease (P > .18 for interaction for all).
No Interaction of Treatment With Mutation Status
PIK3CA mutation status did not appear to predict response to irinotecan plus 5-FU/leucovorin therapy compared with 5-FU/leucovorin therapy (P > .16 for interaction for all). Hazard ratios for the mutant vs wild-type groups on multivariate analysis were 0.70 (95% CI = 0.37–1.31), 0.75 (95% CI = 0.43–1.31), and 0.72 (95% CI = 0.39–1.32) for recurrence-free survival, disease-free survival, and overall survival among patients receiving 5-FU/leucovorin and 1.00 (95% CI = 0.55–1.84), 1.13 (0.65–1.96), and 1.30 (0.72–2.34) for recurrence-free survival, disease-free survival, and overall survival among patients receiving irinotecan plus 5-FU/leucovorin. Outcomes were similar when mutation and wild-type groups were analyzed by treatment.
The investigators concluded, “Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy.”
Research for Cancer and Leukemia Group B 89803 was supported in part by grants from the National Institutes of Health and by Pharmacia & Upjohn Company, now Pfizer Oncology.
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®.
