RT Journal Article
SR Electronic
T1 <em>PIK3CA</em> Mutations in Patients with Advanced Cancers Treated with PI3K/AKT/mTOR Axis Inhibitors
JF Molecular Cancer Therapeutics
JO Mol Cancer Ther
FD American Association for Cancer Research
SP 558
OP 565
DO 10.1158/1535-7163.MCT-10-0994
VO 10
IS 3
A1 Janku, Filip
A1 Tsimberidou, Apostolia M.
A1 Garrido-Laguna, Ignacio
A1 Wang, Xuemei
A1 Luthra, Rajyalakshmi
A1 Hong, David S.
A1 Naing, Aung
A1 Falchook, Gerald S.
A1 Moroney, John W.
A1 Piha-Paul, Sarina A.
A1 Wheler, Jennifer J.
A1 Moulder, Stacy L.
A1 Fu, Siqing
A1 Kurzrock, Razelle
YR 2011
UL http://mct.aacrjournals.org/content/10/3/558.abstract
AB Preclinical data suggest that PIK3CA mutations predict response to PI3K/AKT/mTOR inhibitors. Concomitant KRAS or BRAF mutations may mediate resistance. Therefore, tumors from patients referred to the phase I program for targeted therapy starting in October 2008 were analyzed for PIK3CA mutations using PCR-based DNA sequencing of exons 9 and 20. Consecutive patients with diverse tumor types and PIK3CA mutation were treated whenever possible with agents targeting the PI3K/AKT/mTOR pathway. Overall, PIK3CA mutations were detected in 25 of 217 patients (11.5%; exon 9, n = 11; exon 20, n = 14). In tumor types with more than 10 patients tested, PIK3CA mutations were most frequent in endometrial (3 of 14, 21%), ovarian (5 of 30, 17%), colorectal (9 of 54, 17%), breast (2 of 14, 14%), cervical (2 of 15, 13%), and squamous cell cancer of the head and neck (1 of 11, 9%). Of the 25 patients with PIK3CA mutations, 17 (68%) were treated on a protocol that included a PI3K/AKT/mTOR pathway inhibitor, and 6 (35%) achieved a partial response. In contrast, only 15 of 241 patients (6%) without documented PIK3CA mutations treated on the same protocols responded (P = 0.001). Of the 17 patients with PIK3CA mutations, 6 (35%) had simultaneous KRAS or BRAF mutations (colorectal, n = 4; ovarian, n = 2). Colorectal cancer patients with PIK3CA and KRAS mutations did not respond to therapy, whereas both ovarian cancer patients with PIK3CA and KRAS or BRAF mutations did. In conclusion, PIK3CA mutations were detected in 11.5% of patients with diverse solid tumors. The response rate was significantly higher for patients with PIK3CA mutations treated with PI3K/AKT/mTOR pathway inhibitors than for those without documented mutations. Mol Cancer Ther; 10(3); 558–65. ©2011 AACR. This article is featured in Highlights of This Issue, p. 373