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Olaparib prolongs overall survival in metastatic castration-resistant prostate cancer

Key clinical point: Olaparib led to a significantly longer overall survival (OS) than enzalutamide or abiraterone plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) who had tumors with at least 1 alteration in BRCA1, BRCA2, or ATM genes.

Major finding: The median duration of OS was 19.1 months with olaparib and 14.7 months with control therapy. The risk for death was significantly lower with olaparib therapy (hazard ratio, 0.69; P = .02).

Study details: In this open-label, phase 3 PROfound trial, patients with mCRPC were randomly assigned to receive olaparib (n = 256) or enzalutamide or abiraterone plus prednisone (control therapy; n = 131).

Disclosures: This study was supported by AstraZeneca and Merck Sharp & Dohme (a subsidiary of Merck). The lead author reported receiving grants and personal fees from AstraZeneca.

Commentary

PARP inhibition in tumors with alterations in homologous recombination repair (HRR) genes leads to a “synthetic lethal” effect on prostate cancer cells. In the PROfound study, participants with disease progression of prostate cancer that exhibited an alteration in at least one of 15 HRR genes were randomized to olaparib versus physician’s choice of enzalutamide or abiraterone. Olaparib was associated with improved median overall survival in a cohort that included tumors with alterations in BRCA1, BRCA2, or ATM. In a second cohort where prostate cancers exhibited an alteration in any of the other 12 genes, olaparib was associated with a trend towards overall survival that was not statistically significant (hazard ratio 0.96). The study was not designed to evaluate overall survival on an individual gene level. This study supports the testing of prostate tumors for presence of HRR gene alterations to determine if olaparib may be of benefit for these patients.”

Mark Klein, MD

Citation:

Hussain M et al. N Engl J Med. 2020 Sep 20. doi: 10.1056/NEJMoa2022485.