In the phase II TOPARP-B trial—reported by Joaquin Mateo, MD, in The Lancet Oncology—investigators found that olaparib showed good activity in men with metastatic castration-resistant prostate cancer and DNA damage response (DDR) gene aberrations who had received one or two prior taxane regimens.
In the multicenter trial, 92 evaluable patients were randomly assigned to receive olaparib at 400 mg twice daily (n = 46) or 300 mg twice daily (n = 46) continuously in 4-week cycles until disease progression or unacceptable toxicity.
Joaquin Mateo, MD
The primary endpoint was composite confirmed response, defined as any of radiologic objective response on Response Evaluation Criteria in Solid Tumors, version 1.1; reduction in prostate-specific antigen (PSA) of ≥ 50% from baseline; or conversion of circulating tumor cell count from ≥ 5 cells/7.5 mL blood at baseline to < 5 cells/7.5 mL.
Median follow-up was 24.8 months. Confirmed response was achieved in 54.3% of patients in the 400-mg cohort and 39.1% in the 300-mg cohort. Response rates were 24.2% and 16.2% for radiologic response, 37.0% and 30.2% for PSA response, and 53.6% and 48.1% for circulating tumor cell count conversion response.
Median radiographic progression-free survival was 5.5 months in the 400-mg cohort and 5.6 months in the 300-mg cohort. Median overall survival was 14.3 months and 10.1 months.
The most common grade 3 or 4 adverse event in both cohorts was anemia (reported in 31% of the 300-mg cohort and in 37% of the 400-mg cohort). Serious adverse events occurred in 13% of patients, with the most common being anemia (11%). An adverse event considered possibly related to treatment led to death in one patient (myocardial infarction after 11 days of treatment).
The investigators concluded, “Olaparib has antitumor activity against metastatic castration-resistant prostate cancer with DDR gene aberrations, supporting the implementation of genomic stratification of metastatic castration-resistant prostate cancer in clinical practice.” ■