The combination of olaparib (Lynparza), a PARP inhibitor, and abiraterone (Zytiga), a next generation hormonal agent (NHA), improved radiographic progression free survival (rPFS) compared with abiraterone alone as a first-line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). Researchers presented the results from the PROpel study (Abstract 11) at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California.
“PROpel is the first phase 3 study to evaluate the combined effect of PARP inhibition plus an NHA in the first-line setting of mCRPC irrespective of [homologous recombination repair (HRR)] status,” said Fred Saad, MD, Professor and Chief of Urology at the University of Montreal Hospital Center in Canada, and lead author of the study.
“Olaparib plus abiraterone led to a significant, and I believe clinically meaningful, improvement in rPFS against an active control of abiraterone plus placebo. This benefit led to what I think is the longest rPFS we have seen to date in metastatic CRPC, beyond two years,” Dr. Saad continued.
In clinical care, approximately half of mCRPC patients receive only one line of active therapy and have a median survival of less than two years. However, a phase II trial showed improved rPFS with olaparib and abiraterone versus abiraterone and a placebo in mCRPC patients not separated by HRR mutational status and who had been previously treated with docetaxel. Both olaparib and abiraterone are approved by the U.S. Food and Drug Administration as individual treatments for mCRPC.
In the PROpel study, researchers from more than 15 countries, including the United States, Canada, and Australia, randomly assigned 399 patients to receive olaparib and abiraterone and 397 to placebo and abiraterone. The interim analysis showed that the combination therapy significantly prolonged rPFS regardless of patients’ HRR mutational status, with a median of 24.8 months in the olaparib/abiraterone arm compared with 16.6 months in the placebo/abiraterone arm.
The most common grade 3 or higher adverse event reported in each arm was anemia, at 15.1% and 3.3%, respectively.
Further analysis will assess overall survival (OS).
Celestia S. Higano, MD, the discussant at the ASCO session in which the results were presented said she would wait on the OS results before determining whether to use the combination therapy.
“I think we should wait for the OS data before using the combination, as there is drug and financial toxicity with the combination. However, I will say that I think the rPFS appears to be quite outstanding,” said Dr. Higano, who is an adjunct professor of urology at the University of British Columbia.
Dr. Saad reported relationships with several companies, including AstraZeneca, Janssen Oncology, and Merck. Dr. Higano reported former employment with CTI BioPharma Corp and relationships with many companies, including AstraZeneca, Genentech, and Merck.