Highlights
- •Adverse events (AEs) associated with ipatasertib plus abiraterone were manageable and reversible.
- •AEs appeared rapidly after the initiation of treatment and with limited recurrence.
- •Prophylactic measures can reduce the impact of AEs, as in other studies of ipatasertib.
Abstract
Purpose
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).
Materials and methods
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.
Results
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.
Conclusions
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.
Keywords
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Article info
Publication history
Published online: January 06, 2023
Accepted:
January 2,
2023
Received:
November 16,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
S.B. and C.N.S. contributed equally to the work.
Identification
Copyright
© 2023 Published by Elsevier Inc.
