NEW YORK – AstraZeneca and Merck announced on Friday that in the Phase III PROfound trial metastatic castrate-resistant prostate cancer patients with BRCA 1/2 or ATM mutations lived longer on the PARP inhibitor olaparib (Lynparza) compared to those on enzalutamide (Pfizer/Astellas' Xtandi) or abiraterone (Janssen's Zytiga).
Metastatic castration-resistant prostate cancer is a difficult-to-treat cancer and patients have a poor prognosis. According to a statement from AstraZeneca and Merck, the companies will present detailed overall survival findings at an upcoming medical conference. But, they decided to make an early announcement that PROfound had met this secondary endpoint, since "overall survival in metastatic castration-resistant prostate cancer has remained extremely challenging to achieve," José Baselga, executive VP of oncology R&D at AstraZeneca, said in a statement.
Researchers last year reported at the European Society for Medical Oncology's annual meeting that PROfound had met its primary endpoint. Specifically, olaparib reduced the risk of disease progression by 66 percent in this molecularly defined subset of patients. The drug also improved radiographic progression-free survival in prostate cancer patients with homologous recombination repair gene mutations.
Based on the strength of this data, the US Food and Drug Administration earlier this year accepted a supplemental new drug application for olaparib as a treatment for metastatic castration-resistant prostate cancer patients who have progressed on a new hormonal agent, and have deleterious or suspected deleterious mutations in more than a dozen genes involved in homologous recombination repair, including BRCA1/2 or ATM. The drug's sponsors expect to hear back from the agency in the second quarter of 2020.
The safety and tolerability profile of olaparib was consistent with previous trials, and 16 percent of patients in the olaparib arm and 9 percent of patients in the hormone agent arm discontinued treatment due to adverse effects.
The FDA has previously approved olaparib in a number of molecularly defined cancer indications, including for first-line maintenance therapy of BRCA1/2-mutated advanced ovarian cancer; for advanced germline BRCA1/2-mutated ovarian cancer; for germline BRCA1/2-mutated, HER2-negative metastatic breast cancer; and for first-line maintenance treatment of metastatic pancreatic cancer with germline BRCA1/2 mutations.