AstraZeneca and MSD (Merck) have reported that Lynparza (olaparib) reduced the risk of death by 31% in men with metastatic castration-resistant prostate cancer (mCRPC) in a Phase III PROfound clinical trial.
Lynparza is a PARP inhibitor that acts as a targeted treatment to block DNA damage response in cells/tumours with a deficiency in homologous recombination repair (HRR), including BRCA1/2.
AstraZeneca and MSD partnered in July 2017 to jointly develop and commercialise Lynparza, as well as Koselugo (selumetinib), for the treatment of various cancers.
PROfound results showed that Lynparza exhibited a statistically significant and clinically meaningful improvement in overall survival (OS) compared to enzalutamide or abiraterone in BRCA1/2 or ATM gene-mutated mCRPC patients.
The trial included patients who had progressed on previous treatment with new hormonal agent (NHA) therapies, including enzalutamide and abiraterone.
Lynparza improved OS to a median of 19.1 months against 14.7 months with enzalutamide or abiraterone. This is in spite of 66% of men on NHA treatments switching to Lynparza after progression in the disease condition.
Furthermore, an exploratory analysis revealed a non-statistically significant improvement in OS in overall trial subjects with HRR gene mutations, mitigating the fatal risks by 21% with Lynparza versus NHA treatments.
This analysis showed median OS of 17.3 months in study drug group, against 14 months for enzalutamide or abiraterone.
MSD Research Laboratories chief medical officer Roy Baynes said: “These results further underpin the importance of genomic testing for HRR gene mutations to identify this at-risk patient population and help physicians make treatment decisions.
“These results demonstrate the potential of Lynparza for metastatic castration-resistant prostate cancer patients with certain HRR mutations.”
In August last year, the companies reported that the Phase III PROfound trial met its primary endpoint with significant improvement in radiographic progression-free survival (rPFS) in men with BRCA1/2 or ATM genes.
In May this year, the US Food and Drug Administration (FDA) approved Lynparza for treatment in HRR mutated prostate cancer.