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1164 Alpelisib for PIK3CA-mutated advanced gynecological cancers: first clues of clinical activity
  1. Anna Passarelli1,
  2. Maria Vittoria Carbone2,
  3. Sandro Pignata3,
  4. Roberta Mazzeo4,
  5. Domenica Lorusso5,
  6. Giovanni Scambia5,
  7. Stefania Canova6,
  8. Teresa Di Palma7,
  9. Giulia Tasca8,
  10. Mara Mantiero9,
  11. Emanuele Naglieri10,
  12. Claudia Andreetta11,
  13. Martina Rauso12,
  14. Anna Elisabetta Brunetti13,
  15. Letizia Laera14,
  16. Chiara Abeni15,
  17. Giuseppa Scandurra16,
  18. Anna Rita Gambaro17,
  19. Alessia Pastore18,
  20. Carmelo Bengala19,
  21. Marco Gunnellini20,
  22. Alberto Farolfi21,
  23. Maurizio Spinello22 and
  24. Michele Bartoletti23
  1. 1Department of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, Italy, Napoli, Italy
  2. 2Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
  3. 3Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
  4. 4University of Udine, Udine, Italy
  5. 5Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  6. 6Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
  7. 7Oncologia Medica, Ospedale S Maria Goretti, Latina, Italy, Latina, Italy
  8. 8Veneto Institute of Oncology IOV – IRCCS, Padua, Italy
  9. 9National Cancer Institute of Milan, Milan, Italy
  10. 10IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy
  11. 11Department of Medical Oncology, ‘S. Maria della Misericordia’ University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Udine, Italy
  12. 12Oncological Medical and Specialists Department, Oncology Unit, University Hospital of Ferrara, Ferrara, Italy, Ferrara, Italy
  13. 13Oncological Medical and Specialists Department, Oncology Unit, University Hospital of Ferrara, Ferrara, Italy, Taranto, Italy
  14. 14Department of medical oncology, Miulli General Regional Hospital, Acquaviva delle Fonti, Italy, Acquaviva Delle Fonti, Italy
  15. 15Department of Clinical Oncology, Fondazione Poliambulanza, Brescia, Italy, Brescia, Italy
  16. 16Medical Oncology unit, Cannizzaro Hospital, Catania, Catania, Italy
  17. 17Medical Oncology Unit, ASST Fatebenefratelli Sacco, Ospedale Sacco Polo Universitario, Milano, Milano, Italy
  18. 18S.C. di Oncologia, Azienda Ospedaliera S. Anna, Como, Como, Italy
  19. 19Medical Oncology Unit, Misericordia HOspital Grosseto, Grosseto, Italy
  20. 20UO Oncologia, Ospedale di Gubbio, Gualdo Tadino, Gubbio, Gubbio, Italy
  21. 21IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST), Meldola, Italy
  22. 22Novartis farma S.p.A., Milano, Italy
  23. 23Department of Medical Oncology, Istituto Nazionale Tumori, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Emilia-Romagna, Italy, Mendola, Italy


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.

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