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Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity
Anna Passarelli1, Vittoria Carbone2, Sandro Pignata1
1Department of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, Italy.
Objective:
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.
Methods:
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%; 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).
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.
Insights
Alpelisib shows promise in treating recurrent gynecological cancers with PIK3CA mutations. This study found objective response and disease control rates supporting its use as a targeted therapy for these difficult-to-treat tumors.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Recurrent gynecological cancers, including endometrial and ovarian cancers, present significant unmet clinical needs.
- The PTEN-AKT-PI3K pathway is frequently dysregulated in these malignancies, making it a viable therapeutic target.
- Alpelisib, an approved PI3K inhibitor for PIK3CA-mutated breast cancer, offers a potential treatment avenue.
Purpose of the Study:
- To evaluate the efficacy and safety of alpelisib in patients with recurrent, PIK3CA-mutated gynecological cancers.
- To determine the objective response rate (ORR) and disease control rate (DCR) as primary endpoints.
- To explore the activity of alpelisib in a prospectively treated cohort.
Main Methods:
- A prospective study involving 36 patients with advanced, PIK3CA-mutated gynecological cancers.
- Patients received alpelisib 300 mg orally once daily.
- Tumor response was assessed by objective response rate (ORR) and disease control rate (DCR).
Main Results:
- The study included patients with endometrial (47%), ovarian (28%), and other gynecological cancers (25%).
- Overall ORR was 28% and DCR was 61%.
- Endometrial cancer patients showed the highest response rates (35% ORR, 71% DCR).
Conclusions:
- Alpelisib demonstrates activity in recurrent gynecological cancers harboring PIK3CA mutations.
- These results advocate for biomarker-driven clinical trials of PI3K inhibitors in gynecological oncology.
- Alpelisib represents a potential targeted therapy option for this patient population.
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