Reference Detail

Ref Type

Journal Article

PMID

(38518529)

Authors

Passarelli A, Carbone V, Pignata S, Mazzeo R, Lorusso D, Scambia G, Canova S, Di Palma T, Tasca G, Mantiero M, Naglieri E, Andreetta C, Rauso M, Brunetti AE, Laera L, Abeni C, Scandurra G, Gambaro AR, Pastore A, Bengala C, Gunnellini M, Farolfi A, Spinello M, Bartoletti M

Title

Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Gynecologic oncology	183		2024 Apr	61-67	Gynecol Oncol

URL

Abstract Text

Recurrent gynecological tumors (e.g., 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.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.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%; other, 56%), and presented with visceral metastases at baseline (82%, 70%, and 56%, respectively). Overall, 17 different PIK3CA mutations were found, including 53% in the kinase domain (most commonly H1047R) and 36% in the helical domain (most commonly E545K). Overall, the ORR was 28% and DCR was 61%, with the greatest benefit observed in patients with endometrial cancer (35% and 71%, respectively).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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PIK3CA act mut	female reproductive organ cancer	predicted - sensitive	Alpelisib	Clinical Study	Actionable	In a clinical study, Piqray (alpelisib) treatment was well tolerated and demonstrated activity in patients with advanced gynecologic cancers harboring activating mutations in PIK3CA, resulting in an overall response rate of 28% (10/36, all partial responses), a disease control rate of 61% (22/36), including stable disease in 12 patients, a median duration of response of 13 months, and a median progression-free survival of 6.3 months (PMID: 38518529; NCT04085653).	38518529
PIK3CA act mut	endometrial cancer	predicted - sensitive	Alpelisib	Clinical Study	Actionable	In a clinical study, Piqray (alpelisib) treatment was well tolerated and demonstrated activity in patients with advanced gynecologic cancer harboring activating mutations in PIK3CA and resulted in an overall response rate (ORR) of 28% (10/36), with an ORR of 35% (6/17, all partial responses), disease control rate of 71% (12/17), median duration of response of 13 mo, and median progression-free survival of 7.8 mo in endometrial cancer patients (PMID: 38518529; NCT04085653).	38518529
PIK3CA H1047R	endometrial cancer	predicted - sensitive	Alpelisib	Case Reports/Case Series	Actionable	In a clinical study, Piqray (alpelisib) treatment was well tolerated and demonstrated activity in patients with advanced gynecologic cancer harboring activating mutations in PIK3CA and resulted in an overall response rate (ORR) of 28% (10/36), with an ORR of 35% (6/17, all partial responses) in endometrial cancer patients, including disease control in 7 of 9 patients harboring PIK3CA H1047R (PMID: 38518529; NCT04085653).	38518529