(UroToday.com) In the on-demand poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Cora Sternberg presented an analysis of the nature and manageability of adverse events (AEs) of ipatasertib and abiraterone within the context of the IPATential150 trial (NCT03072238) which compared this combination therapy to abiraterone along as a first-line treatment approach in metastatic castration resistant prostate cancer (mCRPC). To summarize the primary analyses which have been previously presented and published, the combination of ipatasertib and abiraterone significantly reduced the risk of disease worsening or death among patients with PTEN loss by immunohistochemistry (HR, 0.77; 95% CI: 0.61, 0.98; P = 0.034), but not among the entire intention to treat population.
To briefly summarize the methodology, patients with treatment-naïve mCRPC were randomized to ipatasertib and abiraterone or placebo and abiraterone, in addition to prednisone for all patients. As a secondary analysis, the authors performed safety assessments including incidence, severity, and relatedness to the treatment of AEs.
In the overall safety population (n=551 among patients treated with ipatasertib and abiraterone), and in the subset of patients with PTEN loss by IHC (N=263 treated with ipatasertib and abiraterone). The safety profile was similar between these two cohorts: Grade 3-5 AEs were seen in 70% vs 68% and serious AEs were seen in 40% vs 39%, respectively.
Similarly, the safety profile of ipatasertib and abiraterone was comparable among population defined based on Asian ethnicity (n=109 among patients treated with ipatasertib and abiraterone) and non-Asian ethnicity (n=407 among patients treated with ipatasertib and abiraterone): Gr 3-5 AEs, 65% vs 71%; serious AEs, 36% vs 40%, respectively.
The most frequent AEs were asthenia and diarrhea experienced in patients who received placebo and abiraterone (≥20% in n=546) and diarrhea, hyperglycaemia, and rash in those treated with ipatasertib and abiraterone (≥40% in n=551). Further, AEs leading to discontinuation of placebo or ipatasertib occurred in 5% of patients receiving abiraterone and placebo (0 diarrhoea; <1% rash in n=546) and 21% of patients treated with ipatasertib and abiraterone (4% diarrhea; 3% rash in n=551).
The authors, therefore, concluded that the AE profile of ipatasertib and abiraterone is manageable and reversible, and consistent with the phase II A. MARTIN trial. Treatment with ipatasertib and abiraterone was associated with a higher rate of treatment discontinuation.