According to the phase 2 BRCAAway trial, olaparib added to abiraterone/prednisone yielded a longer progression-free survival among patients with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 or ATM mutations, compared with either agent alone or sequentially.

These results were first presented by Maha Hussain, MD, Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois, at the 2024 ASCO GU Cancers Symposium in San Francisco, California.

In this biomarker-preselected, multi-center, phase 2 trial, 165 patients with mCRPC who had not received prior treatment with PARP inhibitors, AR inhibitors, or chemotherapy underwent next generation sequencing and germline testing. Patients with inactivating BRCA1/2 or ATM alterations (n = 61) were randomized on a 1-to-1-to-1 basis. In Arm I patients received abiraterone and prednisone (n = 19); in Arm II patients received olaparib alone (n = 21); and in Arm III patients received olaparib plus abiraterone/prednisone (n = 21). The primary end point of this study was progression-free survival (PFS). Secondary end points included measurable disease response rate, PSA response rate, and toxicity. If patients in Arms I or II progressed, crossover was allowed.

Of the 61 patients with HRR mutations, there were 3 with BRCA1, 46 with BRCA 2, 11 with ATM, and 1 patients with multiple mutations. The median PFS from randomization in Arm I was 8.4 months, in Arm II was 14 months, and in Arm III was 39 months. The objective response rate was 21% in Arm I, 9.5% in Arm II, and 29% in Arm III. The PSA response rate in Arm I was 58%, in Arm II was 67% and in Arm III was 95%. There were 51 patients with treatment-related adverse events. The most common grade 3 of these events were fatigue, anemia, and ALT increases. For Arms I and II, OS was not mature.

Dr Hussain et al concluded, “In mCRPC [patients] with BRCA1/2 or ATM alterations, abiraterone/prednisone plus olaparib was well tolerated and resulted in a longer PFS vs either agent alone or sequentially.”

Source:

Hussain MHA, Kocherginsky M, Agarwal N, et al. BRCAAway: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair mutations (HRRm). Presented at the 2024 ASCO GU Cancers Symposium; January 25-27, 2024; San Francisco. Abstract 19