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Combination Therapy Under Study in Metastatic Prostate Cancer With HRR Mutations

By: Joshua D. Madera, MD
Posted: Tuesday, March 12, 2024

For patients with metastatic castration-resistant prostate cancer with homologous recombination repair (HRR) BRCA1/2 or ATM alterations, combination therapy with olaparib and either abiraterone or prednisone may improve clinical outcomes, according to a the phase II BRCAAway trial results presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium (Abstract 19). Additional investigative efforts are needed to determine the extent of clinical benefit in this patient population, explained Maha H.A. Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center and Northwestern University, Chicago, and colleagues.

A total of 165 patients with metastatic castration-resistant prostate carcinoma were initially recruited for the study. All patients had tumor next-generation sequencing and germline testing performed to assess for BRCA1/2 and ATM alterations. The 61 patients who met the inclusion criteria were randomly assigned to receive treatment with abiraterone plus prednisone (arm 1, n = 19), olaparib alone (arm 2, n = 21), or olaparib plus either abiraterone or prednisone (arm 3, n = 21).

The study findings revealed the median progression-free survival was highest in patients in arm 3 (39.0 months) compared with patients in arm 1 (8.4 months) and arm 2 (14.0 months). Similarly, the objective response rate was increased for patients in arm 3 (29.0%) compared with patients in arm 1 (21.0%) and arm 2 (9.5%). Moreover, the prostate-specific antigen response rate was elevated for patients in arm 3 (95.0%) compared with patients in arm 1 (58.0%) and arm 2 (67.0%). Furthermore, the most common treatment-related adverse events experienced by patients included fatigue (n = 3), increases in liver biomarkers (n = 2), and anemia (n = 2).

Disclosure: For full disclosures of the study authors, visit coi.asco.org.


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