Abstract 1279: Loss of PTEN expression in patients treated with PI3K/AKT/mTOR signaling pathway inhibitors

Abstract

Abstract Background: Loss of PTEN function results in increased PI3K/AKT/mTOR signaling and may predict sensitivity to drugs targeting the PI3K/AKT/mTOR pathway. Methods: Archival tumor samples from patients (N = 202) with diverse cancers referred to the Clinical Center for Targeted Therapy from October 2009 were tested for cytoplasmatic expression of PTEN on immunohistochemistry. Whenever possible, tumor tissue was also analyzed for PIK3CA, RAS (K-, N-), and BRAF mutations using PCR-based DNA sequencing. Consecutive patients with loss of PTEN expression and any tumor type were treated whenever possible with agents targeting the PI3K/AKT/mTOR signaling pathway. Results: Overall, 49 (24%) of 202 patients had loss of PTEN expression. In specific tumor types with a minimum of five patients tested, the loss of PTEN expression was most frequent in squamous cell cervical (60%, 3/5 patients), non-small-cell lung (50%, 4/8), renal (50%, 3/6), uterine (41%, 7/17), gastroesophageal junction/gastric (38%, 3/8), breast cancers (25%, 2/8), melanomas (22%, 6/27), and colorectal cancers (20%, 6/30). Tumors with PTEN loss had frequencies of simultaneous mutations in PIK3CA, RAS (K-, N-), BRAF that were similar to patients with PTEN expression. Of the 49 patients with PTEN loss, 29 (median number of prior therapies, 3) were treated on a protocol that included a PI3K/AKT/mTOR pathway inhibitor. Six of these 29 patients (20.5%) achieved a partial response (PR) (2 uterine cancers, 1 squamous cell cervical cancer; 1 squamous cell head and neck cancer; 1 melanoma; 1 renal cancer) and 8 (27.5%) had stable disease (SD) for >/ = 4 months (total SD>/ = 4 months + PR = 48%). These 29 treated patients had a median progression-free survival of 4.3 months (95% CI, 3.4-5.2). Conclusion: Loss of PTEN expression was found in 24% of patients with various solid tumors. Fourteen of 29 heavily-pretreated patients (48%) had a PR or SD >/ = 4 months, when treated with a PI3K/AKT/mTOR axis inhibitor, suggesting that matching patients with these inhibitors based on PTEN loss merits further exploration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1279. doi:10.1158/1538-7445.AM2011-1279