1164 Alpelisib for PIK3CA-mutated advanced gynecological cancers: first clues of clinical activity

Introduction/Background Recurrent gynecological tumors (eg, endometrial and ovarian cancers) are incurable diseases; therefore, new treatment options are urgently needed. The PTEN-AKT-PI3K pathway is frequently altered in these tumors, representing a potential treatment target. Alpelisib is an α-specific PI3K inhibitor approved in PIK3CA-mutated advanced breast cancer. We report outcomes from a large series of patients with PIK3CA-mutated gynecological cancers prospectively treated with alpelisib within a controlled program. Methodology From April 2021 to December 2022, 36 patients with PIK3CA-mutated advanced gynecological cancers received alpelisib 300 mg orally once daily. Objective response (ORR) and disease control (DCR) rates provided measure of the antitumor activity of alpelisib, the primary objective of the study. Results Included patients had endometrial (17/36 47%), ovarian (10/36 28%), or other gynecological cancers (9/36 25%). Most patients had received 2–3 prior systemic treatments (endometrial, 47·2%; ovarian, 60·0%; other, 55·6%), and presented with visceral metastases at baseline (82·0%, 70·0%, and 56·0%, respectively). Overall, 17 different PIK3CA mutations were found, including 52·7% in the kinase domain (most commonly H1047R) and 36·1% in the helical domain (most commonly E545K). The ORR was 27·7% and DCR was 70·0%, with the greatest benefit observed in patients with endometrial cancer (35·0% and 70·0%, respectively). Conclusion Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers. Disclosures This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.