Olaparib in Patients With Metastatic Prostate Cancer With BRCA1/2 Mutation: Results From the TAPUR Study.

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.

• Authors: Eddy S Yang, Susan Halabi, Michael Rothe, Elizabeth Garrett-Mayer, Pam K Mangat, Evan Pisick, Elie Dib, Earle F Burgess, Michael Zakem, Nitin Rohatgi, Mehmet A Bilen, Raegan O'Lone, Gina N Grantham, Richard L Schilsky
• Journal: JCO precision oncology (JCO Precis Oncol) Vol. 7 Pg. e2200505 (02 2023) ISSN: 2473-4284 [Electronic] United States
• PMID: 36753688 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• BRCA1 Protein
• BRCA1 protein, human
• olaparib
• Phthalazines

Topics

• Humans
• Male
• Antineoplastic Agents (therapeutic use)
• BRCA1 Protein (genetics)
• Mutation
• Phthalazines (adverse effects)
• Prostatic Neoplasms, Castration-Resistant (drug therapy, genetics, pathology)