Metastatic Castration-Resistant Prostate Cancer: Reconsidering the Role of Olaparib
Posted: Monday, August 30, 2021
Clinical responses to PARP inhibition versus standard chemotherapy may vary based upon select homologous recombination DNA repair deficiencies (HRRs) in patients with metastatic-resistant prostate cancer who exhibit disease progression following androgen inhibition. Daniel E. Spratt, MD, of Vanderbilt University Medical Center, Nashville, and colleagues conducted a network analysis of the PROfound and CARD clinical trials to identify which DNA variants were associated with better treatment outcomes following novel PARP inhibition (olaparib) or chemotherapy (cabazitaxel).
“While treatment with olaparib was associated with superior radiographic progression-free survival in patients with BRCA1/2 variants, those with other HRR variants may have worse outcomes with this approach, which should be reassessed by national guidelines,” stated the investigators. Their study findings were published in a research letter in JAMA Network Open.
A systematic review was conducted using clinical trials that enrolled patients with metastatic castration-resistant prostate cancer who exhibited disease progression following androgen inhibition. Treatment outcomes in patients in the PROfound trial (n = 387) who received olaparib and patients in the CARD trial (n = 255) who received cabazitaxel were compared with outcomes in control patients from other trials. These control patients had received cabazitaxel or PARP inhibition, and overall survival and radiographic progression-free survival following androgen inhibition were reported.
Patients with BRCA1, BRCA2, or ATM variants, specifically those who had received taxanes, were found to have a 78% higher probability of progression-free survival when treated with olaparib, compared with cabazitaxel (hazard ratio [HR] = 0.52, 95% confidence interval = 0.32–0.84, P = .007). However, in patients with 12 other HRR variants (including CDK12, CHECK1/2, PALB2, and RAD51C/D), cabazitaxel was associated with an 83% probability of superior progression-free survival compared with olaparib. Overall survival was not significantly different across groups, although in patients who did not receive taxanes, the estimated superiority of cabazitaxel versus olaparib was 60% to 80%.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
