Olaparib and Abiraterone Combination Found Effective for Stage 4 Prostate Cancer Treatment

In research by Clarke and colleagues presented at the 2018 ASCO Annual Meeting, for metastatic and hormone suppression-resistant prostate cancer, olaparib (Lynparza) combined with abiraterone showed better outcomes than standard abiraterone (Zytiga) alone.

Previously treated metastatic and castration-resistant prostate cancer patients, totaling 142, entered this multicenter phase-2 clinical trialand were randomized: one group received standard abiraterone (Zytiga)alone, the other combined it with olaparib (Lynparza) . The study was selected as Best of ASCO and published in The Lancet Oncology.

The primary endpoint was radiographic progression-free survival (duration of disease control with treatment). Secondary endpoints included time to second progression or death, overall survival and health-related quality of life.

Lead author Professor of Urological Oncology Noel Clarke says: “This is the first study showing additional benefit from abiraterone plus olaparib, a PARP inhibitor, in metastatic castration-resistant prostate cancer, and this positive result appears independent of BRCA mutation status. The data suggest a promising new treatment approach for this aggressive disease.”Study resultsMedian radiographic progression-free survival was 8.2 months with abiraterone alone and 13.8 with combination. Median time to second progression or death was 23.3 months with combination and 18.5 with monotherapy. Median overall survival was 22.7 months with combination and 20.9 with abiraterone alone. The first two differences were statistically significant, but overall survival was not.

Because not all patients’ BRCA status was known before the study, subgroup analysis could not show whether mutation-positive patients responded better.

Grade 3 or more severe side effects and treatment discontinuations were more frequent with combination. The commonest grade 3 or higher effects were anemia (% 21), pneumonia (% 6) and myocardial infarction (% 6). Serious cardiovascular events occurred in 7 combination patients and 1 abiraterone-only patient.

Conclusion / Comment

BRCA genes repair DNA, and mutations reduce repair capacity. PARP inhibitors are new treatments blocking DNA repair, mainly effective in BRCA-positive cancers. Olaparib showing prostate cancer activity regardless of BRCA status makes this study noteworthy. However, adding olaparib increased side effects without significantly prolonging overall survival, suggesting more studies are needed before this combination becomes a standard for metastatic castration-resistant prostate cancer.