RESUMEN
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.
Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I , Neoplasias de los Genitales Femeninos , Mutación , Tiazoles , Humanos , Femenino , Fosfatidilinositol 3-Quinasa Clase I/genética , Persona de Mediana Edad , Anciano , Neoplasias de los Genitales Femeninos/genética , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/patología , Adulto , Tiazoles/uso terapéutico , Tiazoles/administración & dosificación , Anciano de 80 o más Años , Neoplasias Endometriales/genética , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Estudios Prospectivos , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Inhibidores de las Quinasa Fosfoinosítidos-3/administración & dosificaciónRESUMEN
Purpose: During the last decade, [18F]F-choline positron emission tomography (PET) had a rising role in prostate cancer (PCa) imaging. However, despite auspicious premises, [18F]F-choline PET is not currently recommended for the evaluation of response to therapy assessment in PCa, mainly due to the lack of large-scale prospective trials. Methods: We report the cases of seven patients affected by PCa, in which [18F]F-choline PET (either with computed tomography-CT or magnetic resonance imaging-MR) contributed significantly in the systemic therapy response evaluation. Results and conclusion: [18F]F-choline PET/CT or PET/MR demonstrated to be a useful imaging modality in the assessment of response to systemic therapy in metastatic PCa patients, irrespective of the stage of disease (either in hormone sensitive and in castrate resistant condition) and the kind of systemic treatment. In most cases, PSA serum values and [18F]F-choline PET showed a synchronous disease evolution after systemic therapy. ADT can alter [18F]F-choline uptake, therefore the time of scan should be correctly planned. Finally, PET/CT with [18F]F-choline is a useful tool for reinforcing the identification of metastatic disease in case of a switch from metastatic castration sensitive to castration resistant PCa.