Abstract LB-446: Target-based therapeutic matching in patients with PIK3CA mutations and PTEN aberrations

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.LB-446-LB-446
• Main Authors: Janku, Filip, Wheler, Jennifer J., Piha-Paul, Sarina A., Stepanek, Vanda M., Fu, Siqing, Hong, David S., Naing, Aung, Falchook, Gerald S., Moulder, Stacy L., Luthra, Rajyalakshmi, Tsimberidou, Apostolia M., Kurzrock, Razelle
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-LB-446

Background: Activating mutations of PIK3CA or loss of PTEN function result in increased PI3K/AKT/mTOR signaling and may predict sensitivity to drugs targeting the PI3K/AKT/mTOR pathway, while simultaneous KRAS mutations may mediate resistance. Methods: From 10/2008, available tumor samples from advanced cancer patients referred to the Phase I Clinical Trials Program were screened for PIK3CA mutations and PTEN aberrations (loss of expression on immunohistochemistry or mutation) in a CLIA-certified laboratory. Patients with tumors carrying PIK3CA mutations and/or PTEN aberrations were treated, whenever possible, with agents targeting the PI3K/AKT/mTOR pathway. Results: Overall, 1,540 patients were tested, and 285 (19%) had PIK3CA mutations (n=141), PTEN aberrations (n=130), or a simultaneous PIK3CA mutation and PTEN aberration (n=14). Of these 285 patients, 131 (46%) were treated in clinical trials containing a PI3K/AKT/mTOR inhibitor (median age, 56; median number of prior therapies, 3). Of these 131 patients, 26 (20%, 95% CI 0.14-0.27) achieved a partial response (PR) (4/21 breast cancers; 4/19 endometrial cancers; 3/13 ovarian cancers; 4/9 head and neck cancers; 4/10 cervical cancers; 2/9 renal cancers; 2/4 salivary gland cancers; 1/4 sarcomas; 1/3 non-small cell lung cancers; 1/2 melanomas). Patients without known PIK3CA mutations and/or PTEN aberrations treated on the same protocols had a PR rate of 6% (26/458; 95% CI 0.04-0.08, p=0.0001). Treated patients with wild-type KRAS had a higher PR rate of 20% compared to 8% in patients with simultaneous KRAS mutations (p=0.05). Conclusion: Heavily pretreated patients with PIK3CA mutations and/or PTEN aberrations had higher PR rates on protocols with PI3K/AKT/mTOR inhibitors than patients without these aberrations (20% vs 6%; p = 0.0001). Simultaneous KRAS mutations were associated with a lower PR rate. Screening for PIK3CA mutations and PTEN aberrations merits further evaluation in making treatment decisions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-446. doi:1538-7445.AM2012-LB-446