AstraZeneca and MSD – known as Merck & Co in the US and Canada – have reported final overall survival results from a phase 3 trial of a Lynparza (olaparib) combination in metastatic castration-resistant prostate cancer (mCRPC).
The results from PROpel, presented at this year’s American Society of Clinical Oncology Genitourinary Cancers Symposium, showed the PARP inhibitor in combination with anti-androgen therapy Zytiga (abiraterone) and prednisone or prednisolone was associated with a median overall survival of 42.1 months, compared to 34.7 months for abiraterone plus placebo.
While the increase in median overall survival – the trial’s secondary endpoint – did not achieve statistical significance, the companies said the results ‘build on the meaningful survival gains achieved for patients in this setting treated with abiraterone alone, a current standard of care’.
The combination treatment is already under priority review by the US Food and Drug Administration, based on earlier results from PROpel that demonstrated a reduction in the risk of disease progression or death by 34%.
Prostate cancer is the second most common cancer in male patients and the fifth leading cause of cancer deaths in men globally, with an incidence of 1.4 million and 375,000 deaths in 2020 alone.
Overall survival for patients with mCRPC is around three years in clinical trial settings, but even shorter in the real world, the companies explained.
Lynparza is the first targeted treatment to block DNA damage response in cells and tumours carrying a deficiency in homologous recombination repair, such as those with mutations in BRCA1 and BRCA2.
Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said: “The results in the overall trial population from PROpel illustrate how the combination of Lynparza and abiraterone can exploit the dependency of the androgen receptor’s role in DNA repair on PARP to provide greater anticancer activity than abiraterone alone.
“Based on the totality of the data, it is notable to see this combination delivering a meaningful benefit in a broad population of patients in this setting, which is further underscored by the recent indication approved in the EU.”
Lynparza in combination with abiraterone was approved by the European Commission in December 2022 for certain patients with mCRPC and is currently undergoing regulatory review in other countries.
The drug also holds a number of approvals for a range of indications for ovarian, breast, fallopian tube, peritoneal and pancreatic cancers.