Olaparib in Patients With Metastatic Prostate Cancer With <i>BRCA1</i>/<i>2</i> Mutation: Results From the TAPUR Study
Eddy S. Yang, Susan Halabi, Michael Rothe, Elizabeth Garrett‐Mayer, Pam K. Mangat, Evan Pisick, Elie G. Dib, Earle F. Burgess, Michael Howard Zakem, Nitin Rohatgi, Mehmet Asım Bilen, Raegan O'Lone, Gina N. Grantham, Richard L. Schilsky
Abstract
PURPOSE The TAPUR Study is a phase II basket trial that aims to evaluate activity of approved targeted agents in patients with advanced cancers with potentially actionable genomic variants. Data from a cohort of patients with metastatic castrate-resistant prostate cancer (mCRPC) and BRCA1/ 2 mutations treated with olaparib are reported. METHODS Eligible patients with measurable mCRPC were matched to treatment according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary end point of disease control, defined as objective response or stable disease of at least 16-week duration. Secondary end points include radiographic progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS Thirty patients with mCRPC with BRCA1/ 2 mutations were treated with olaparib. The disease control rate was 69% (95% CI, 51 to 81), and the objective response rate was 58% (95% CI, 37 to 77). The median radiographic progression-free survival and the median overall survival were 38.4 (95% CI, 16.3 to 52.1) weeks and 76.4 (95% CI, 49.3 to 106.0) weeks, respectively. Six of 30 (20%) patients experienced grade 3-4 adverse or serious adverse events including anemia, aspiration, decreased WBC count, and fatigue. CONCLUSION Olaparib has antitumor activity in patients with mCRPC with BRCA1/ 2 mutations and warrants further study to determine how to best integrate it into the standard treatment of patients with BRCA1/ 2-mutated prostate cancer.