Olaparib in metastatic prostate cancer with BRCA1/2 mutations

As many as 28% of patients with metastatic castrate-resistant prostate cancer are found to have germline or somatic alterations in genes involved in the homologous recombination repair pathway, with alterations in BRCA1/2 being most common; results of the phase II TAPUR study, recently published on JCO Precision Oncology, showed that the PARP inhibitor olaparib has antitumor activity in patients with heavily pretreated prostate cancer with BRCA1 or BRCA2 mutations.

The TAPUR Study is a phase II basket study that evaluates the antitumor activity of commercially available targeted agents in patients with advanced cancers with specific genomic alterations. The new paper presents the results of thirty patients with metastatic castrate-resistant prostate cancer and BRCA1/2 inactivating mutations treated with olaparib (twice daily for a total daily dose of 600 mg or 800 mg) until progressive disease or withdrawal because of unacceptable toxicity, patient preference, or physician recommendation to discontinue. The disease control rate was 69% and the objective response rate was 58%; the median radiographic progression-free survival and the median overall survival were 38.4 weeks and 76.4 weeks, respectively. Six of thirty (20%) patients experienced grade 3-4 adverse or serious adverse events including anemia, decreased white blood cells count and fatigue. «Olaparib had antitumor activity in patients with heavily pretreated prostate cancer with BRCA1 or BRCA2 mutations», authors say. «This study provides additional information on the efficacy of olaparib in a representative population of heavily pretreated patients with metastatic castrate-resistant prostate cancer treated largely in the community setting. PARP inhibitors have emerged as an important new class of drugs for the treatment of prostate cancers with homologous recombination DNA repair defects; more work is now needed to refine the biomarkers that can best identify patients most likely to benefit. As new information on the many functions of PARP is uncovered, new combinations are being developed to expand the utility of PARP inhibitors beyond patients with tumors that harbor DNA repair defects; as new clinical trials go forward, it will be crucial to enroll a study population that represents the diverse demographics of people with prostate cancer», authors conclude.