(UroToday.com) The phase 3 PROfound study1 demonstrated improved overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) who had progressed on prior anti-androgen therapy and harbor deleterious alteration in BRCA1BRCA2, and ATM. A radiographic progression-free survival benefit was also demonstrated in an overall group of patients harboring a deleterious alteration in selected homologous recombination (HR) genes. In this abstract, investigators presented results of exploratory analyses examining the relationship between individual gene alterations and clinical outcomes.

Of the 160 patients with BRCA1 or BRCA2 alteration, 128 had only an alteration in BRCA2 and 13 had only an alteration in BRCA1. The remaining patients had co-occurring alterations in other HR genes. 86 patients had alterations in ATM, and 89 had alterations in CDK12. The percentage of patients with these gene alterations that had measurable disease received prior taxane or had specific patterns of metastatic disease (bone only, visceral, other) were well balanced between the olaparib or control arms.

With regards to benefit with alterations in these four genes, patients with BRCA1 and/or BRCA2 alteration seemed to derive the greatest benefit from olaparib relative to control with respect to radiographic progression-free survival (rPFS), overall survival, response rate, PSA response, and circulating tumor cell conversion. Other HR gene alterations were too rare to conduct meaningful analysis on their relationship to clinical outcome. Importantly, RAD51C and FANCLalterations were not present in the PROfound cohort. 

Presented by: Johann de Bono, MD, Ph.D., Regius Professor of Cancer Research and a Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. He is also the Director of the Drug Development Unit

Written by: Alok Tewari, MD, Ph.D., Medical Oncologist at the Dana-Farber Cancer Institute, at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021

1. Hussain M, Mateo J, Fizazi K, et al., Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer N Engl J Med 383, (2020):2345-2357

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