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

Eddy S Yang1, Susan Halabi2, Michael Rothe3

  • 1Department of Radiology, O'Neal Comprehensive Cancer Center at the University of Alabama at Birmingham School of Medicine, Birmingham, AL.

JCO Precision Oncology
|February 8, 2023
PubMed
Abstract

Insights

Olaparib showed significant antitumor activity in patients with metastatic castrate-resistant prostate cancer (mCRPC) harboring BRCA1/2 mutations. Further research is needed to integrate this targeted therapy into standard mCRPC treatment protocols.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Metastatic castrate-resistant prostate cancer (mCRPC) presents a significant clinical challenge.
  • Genomic variants, such as BRCA1/2 mutations, represent potential therapeutic targets in mCRPC.
  • Targeted therapies offer a promising avenue for improving outcomes in patients with specific molecular alterations.

Purpose of the Study:

  • To evaluate the efficacy of olaparib in patients with mCRPC and BRCA1/2 mutations.
  • To assess the antitumor activity and safety of olaparib within the TAPUR (Targeted Agent and Profiling Utilization Registry) study.
  • To determine the disease control rate and response rates for olaparib in this patient population.

Main Methods:

  • A phase II basket trial design was employed, matching patients to targeted agents based on genomic variants.
  • Thirty patients with measurable mCRPC and BRCA1/2 mutations received olaparib.
  • Disease control (objective response or stable disease ≥16 weeks) was the primary endpoint, with secondary endpoints including survival and safety.

Main Results:

  • Olaparib demonstrated a disease control rate of 69% and an objective response rate of 58% in patients with mCRPC and BRCA1/2 mutations.
  • Median radiographic progression-free survival was 38.4 weeks, and median overall survival was 76.4 weeks.
  • Grade 3-4 adverse events occurred in 20% of patients, including anemia and fatigue.

Conclusions:

  • Olaparib exhibits significant antitumor activity in mCRPC patients with BRCA1/2 mutations.
  • These findings support further investigation into the optimal integration of olaparib into the treatment landscape for BRCA1/2-mutated prostate cancer.
  • Targeted therapy with olaparib represents a viable option for select mCRPC patients based on their genomic profile.

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