Olaparib demonstrates activity in prostate cancer with DRR mutations

  • Mateo J & al.
  • Lancet Oncol
  • 2 Dec 2019

  • curated by Dawn O'Shea
  • Medical news
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New findings from the TOPARP-B trial suggest olaparib has antitumour activity against metastatic castration-resistant prostate cancer (mCRPC) carrying DNA damage response (DDR) gene aberrations.

The results of the study, published in the Lancet Oncology, provide support for the implementation of genomic stratification of mCRPC in clinical practice.

The open-label, investigator-initiated, randomised phase 2 trial recruited participants from 17 UK hospitals. Participants were men aged ≥18 yrs, with progressing mCRPC previously treated one or two taxane regimens and an ECOG performance status of ≤2. Patients with DDR gene aberrations were randomly assigned to receive 400 mg or 300 mg olaparib twice daily, given continuously in four-week cycles.

The primary endpoint was confirmed response, defined as a composite of all patients presenting with any of the following: radiological objective response, a decrease in PSA of ≥50% (PSA50), or conversion of circulating tumour cell (CTC) count (from ≥5 cells/7.5 mL to

A total of 161 patients had DDR gene aberrations, 98 of whom were treated, with 92 evaluable for the primary endpoint. Median follow-up was 24·8 months.

Confirmed composite response was achieved in 25 (54.3%; 95% CI 39.0-69.1) of 46 evaluable patients in the 400 mg cohort, and 18 (39.1%; 95% CI 25.1-54.6) of 46 evaluable patients in the 300 mg cohort.

Radiological response was achieved in 8 (24.2%; 11.1-42.3) of 33 and 6 (16.2%; 6.2-32.0) of 37, respectively. PSA50 response was achieved in 17 (37.0%; 23.2-52.5) and 13 (30.2%; 17.2-46.1) respectively, CTC count conversion was achieved in 15 (53.6%; 33.9-72.5) and 13 (48.1%; 28.7-68.1).

Nineteen serious adverse reactions were reported in 13 patients. One possible treatment-related death (myocardial infarction) occurred after 11 days of treatment in the 300 mg cohort.