Data from Pharmawand - Curated by EPG Health - Date added 01 October 2019
AstraZeneca and Merck Inc. presented detailed results from the Phase III PROfound trial in 387 men with metastatic castration-resistant prostate cancer (mCRPC) taking Lynparza (olaparib), who have a mutation in their homologous recombination repair (HRRm) genes and whose disease had progressed on prior treatment with new hormonal agent (NHA) treatments (e.g. abiraterone or enzalutamide). The trial was designed to analyse men with HRRm genes in two cohorts: the primary endpoint was in those with mutations in BRCA1/2 or ATM genes and then, if Lynparza showed clinical benefit, a formal analysis was performed of the overall trial population of men with HRRm genes (BRCA1/2, ATM, CDK12 and 11 other HRRm genes; key secondary endpoint).
Results showed a statistically significant and clinically meaningful improvement with Lynparza in the primary endpoint of radiographic progression-free survival (rPFS), improving the time men with BRCA1/2- or ATM-mutated mCRPC lived without disease progression or death to a median of 7.4 months vs. 3.6 months for those treated with abiraterone or enzalutamide. Lynparza reduced the risk of disease progression or death by 66% (equal to a hazard ratio of 0.34) for these men. The trial also met the key secondary endpoint of rPFS in the overall HRRm population, where Lynparza reduced the risk of disease progression or death by 51% (equal to a hazard ratio of 0.49) and improved rPFS to a median of 5.8 months vs. 3.5 months for abiraterone or enzalutamide.
Results also showed a trend at this interim analysis time point for improvement in overall survival (OS), another key secondary endpoint, in the two groups. Lynparza extended OS to 18.5 months vs.15.1 months for abiraterone or enzalutamide in men with BRCA1/2- or ATM-mutated tumours, despite that at this interim analysis 81% of patients on NHA crossed over to Lynparza at progression. A similar trend in OS was observed at this interim analysis in the overall HRRm population with a median of 17.5 months’ OS for men treated with Lynparza vs. 14.3 months for abiraterone or enzalutamide (analysis at 41% data maturity). The results were presented during the Presidential Symposium at the 2019 European Society of Medical Oncology (ESMO) congress.