PIK3CA Mutation H1047R Is Associated with Response to PI3K/AKT/mTOR Signaling Pathway Inhibitors in Early-Phase Clinical Trials

摘要: PIK3CA mutations may predict response to PI3K/AKT/mTOR inhibitors in patients with advanced cancers, but the relevance of mutation subtype has not been investigated. Patients diverse cancers referred Clinical Center for Targeted Therapy were analyzed and, if possible, KRAS mutations. treated, whenever agents targeting pathway. Overall, 105 (10%) 1,012 tested harbored Sixty-six (median 3 prior therapies) PIK3CA-mutant patients, including 16 individuals (of 55 tested) simultaneous mutations, treated on a protocol that included pathway inhibitor; 17% (11/66) achieved partial (PR). H1047R compared who had other or wild-type same protocols higher PR rate (6/16, 38% vs. 5/50; 10% 23/174, 13%, respectively; all P ≤ 0.02). None coexisting and codon 12 13 attained (0/16, 0%). combination therapy versus single-agent therapies (11/38, 29% 0/28, 0%; = 0.002). Multivariate analysis showed was only independent factor predicting [OR 6.6, 95% confidence interval (CI), 1.02-43.0, 0.047). Our data suggest interaction between aberrations axis warrants further exploration.