Adding ipatasertib to abiraterone and prednisone/prednisolone significantly improved radiographic progression-free survival for patients with metastatic castration-resistant prostate cancer (mCRPC) with PTEN-loss tumours by immunohistochemistry in the IPATential150 trial (NCT03072238). Here we characterise the safety of these agents in subpopulations and assess manageability of key adverse events (AEs).
In this randomised, double-blind, phase 3 trial, patients with previously untreated asymptomatic or mildly symptomatic mCRPC were randomised 1:1 to receive ipatasertib-abiraterone or placebo-abiraterone (all with prednisone/prednisolone). AEs were analysed, focusing on key AEs of diarrhoea, hyperglycaemia, rash and transaminase increased.
1097 patients received study medication and were assessed for safety (47% with PTEN-loss tumours by immunohistochemistry and 20% were Asian). Ipatasertib was associated with increased Grade 3/4 AEs and AEs leading to treatment discontinuation vs placebo. The rate of discontinuation of ipatasertib was 18% in patients with PTEN-loss and 21% overall. The frequencies of all-grade, Grade 3/4 and serious AEs were similar between the PTEN-loss and overall populations. Diarrhoea, hyperglycaemia, rash and transaminase elevation were more frequent in ipatasertib-treated patients, appearing rapidly after treatment initiation (median onset: 8-43 days for ipatasertib arm and 56-104 days for placebo). The ipatasertib discontinuation rate was 32% and 18% in Asian and non-Asian patients, respectively, despite similar baseline characteristics and Grade 3/4 AE frequencies between groups.
Ipatasertib plus abiraterone had an overall tolerable safety profile consistent with known toxicities. More AEs leading to drug discontinuation were observed with ipatasertib than placebo, but incidence would likely be lessened with prophylactic measures.
Clinical genitourinary cancer. 2023 Jan 07 [Epub ahead of print]
Nobuaki Matsubara, Johann de Bono, Christopher Sweeney, Kim N Chi, David Olmos, Shahneen Sandhu, Christophe Massard, Josep Garcia, Geng Chen, Adam Harris, Fanny Schenkel, Rucha Sane, Healther Hinton, Sergio Bracarda, Cora N Sternberg
Division of Breast and Medical Oncology, National Cancer Center Hospital East, Chiba, Japan. Electronic address: ., The Institute of Cancer Research and the Royal Marsden Hospital, London, UK., Dana-Farber Cancer Institute, Boston, MA., BC Cancer Agency, Vancouver, Canada., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain., Peter MacCallum Cancer Centre, Melbourne, Australia., Gustave Roussy, Villejuif, France., F. Hoffmann-La Roche, Ltd., Basel, Switzerland., Genentech, South San Francisco, CA., Medical Oncology, Azienda Ospedaliera Santa Maria-Terni, Terni, Italy. Electronic address: ., Englander Institute for Precision Medicine, Weill Cornell Medicine, Sandra and Edward Meyer Cancer Center, NewYork-Presbyterian, New York, NY. Electronic address: .