— Median overall survival with olaparib plus abiraterone reached 68 months in mid-stage trial
February 27, 2026
• 3 min read
SAN FRANCISCO — The first-line combination of olaparib (Lynparza) plus abiraterone (Zytiga) led to a significant overall survival (OS) advantage for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 or ATM alterations in a small phase II study.
Median OS reached 68 months with olaparib plus abiraterone and prednisone, as compared with 28 months with abiraterone and prednisone alone (HR 0.39, 95% CI 0.16-0.93) and 37 months with olaparib alone (HR 0.51, 95% CI 0.22-1.18), reported Maha Hussain, MD, of Northwestern University’s Feinberg School of Medicine in Chicago.
OS rates at 60 months were 55%, 31%, and 42%, respectively, according to updated results from the BRCAAway trial presented at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.
Initial results of the study showed that adding olaparib to abiraterone and prednisone significantly improved progression-free survival (PFS) compared with abiraterone/prednisone or olaparib alone. In updated data, median PFS was 39 months with olaparib plus abiraterone/prednisone versus 8.6 months with abiraterone/prednisone (HR 0.33, 95% CI 0.15-0.72) and 14 months with olaparib (HR 0.37, 95% CI 0.17-0.84).
ASCO discussant Evan Y. Yu, MD, of the University of Washington and Fred Hutchinson Cancer Center in Seattle, noted that while the trial’s OS and PFS results with olaparib plus abiraterone were “very impressive,” the small study was limited by the “potential for imbalances.”
For example, 47% of patients in the abiraterone/prednisone arm had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 compared with 29% of patients in the olaparib-alone arm and 24% in the olaparib/abiraterone/prednisone arm. Other differences included the proportions of patients with visceral disease and BRCA2 mutations.
“The numbers aren’t exactly equal as you might see in a larger study,” Yu said.
Is the combination “for everyone with pathogenic BRCA1/2 alteration?” he asked. “I would say no — it’s a small trial and does not adequately address crossover and subsequent therapy issues. However, it builds on a body of evidence for combination therapy and supports the opportunity to give a PARP inhibitor early if you think your patient has really aggressive disease.”
The combination of olaparib plus abiraterone was approved for patients with BRCA-mutated mCRPC, based on findings from the phase III PROpel trial, as is the combination of niraparib plus abiraterone (Akeega), based on results from the phase III MAGNITUDE trial.
In BRCAAway, eligibility criteria included no prior exposure to PARP inhibitors, androgen receptor pathway inhibitors, or chemotherapy for mCRPC. Participants underwent tumor next-generation sequencing and germline testing. Of the 61 patients, median age was 63-69, 86-90% were white, and 10-11% were Black.
Participants were randomized to receive abiraterone 100 mg once daily plus prednisone 5 mg twice daily, olaparib 300 mg twice daily, or olaparib plus abiraterone/prednisone.
Objective response rates were 33% with olaparib and abiraterone/prednisone, 22% in the abiraterone/prednisone arm, and 9.5% in the olaparib-alone arm.
At progression, eight of 19 patients crossed over from abiraterone/prednisone to olaparib, with a response rate of 38%, and eight of 21 crossed over from olaparib to abiraterone/prednisone, with a response rate of 25%.
Regarding safety, anemia, fatigue, gastrointestinal disorders, and nausea occurred in the olaparib arms, but the number of grade 3 treatment-related adverse events was similar across groups — four with abiraterone/prednisone, three with olaparib alone, and four with olaparib/abiraterone/prednisone.
“Overall, treatment was very well tolerated, and some of these patients were literally on treatment for years, so it is remarkable that it was tolerated for that long,” observed Hussain.
