Olaparib Without Androgen Deprivation for Biochemically Recurrent Prostate Cancer Following Prostatectomy (2024)

• ¹Johns Hopkins University School of Medicine, Baltimore, Maryland

• ²University of Nebraska Medical Center, Omaha

• ³Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania

• ⁴Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

• ⁵Veracyte, San Francisco, California

• ⁶University of Minnesota, Minneapolis

Key Points

Question Is olaparib monotherapy effective for patients with high-risk biochemically recurrent prostate cancer in the absence of androgen deprivation therapy?

Findings In this phase 2, single-arm nonrandomized controlled trial of 51 patients, 13 patients (26%) had a confirmed 50% or higher decline in prostate-specific antigen from baseline. This varied by the presence of homologous recombination repair alterations, with the greatest benefit being in those with BRCA2 alterations, and the adverse effect profile was consistent with prior studies of olaparib.

Meaning Olaparib without androgen deprivation has activity in certain patients with biochemically recurrent prostate cancer.

Importance Olaparib is a poly(adenosine diphosphate–ribose) polymerase inhibitor that provides benefit in combination with hormonal therapies in patients with metastatic prostate cancer who harbor homologous recombination repair (HRR) alterations. Its efficacy in the absence of androgen deprivation therapy has not been tested.

Objective To determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy.

Design, Setting, and Participants This phase 2, single-arm nonrandomized controlled trial enrolled genetically unselected patients across 4 sites in the US from May 2017 to November 2022. Eligible patients had BCR disease following radical prostatectomy, a prostate-specific antigen (PSA) doubling time of 6 months or shorter, an absolute PSA value of 1.0 ng/mL or higher, and a testosterone level of 150 ng/dL or higher.

Intervention Treatment was with olaparib, 300 mg, by mouth twice daily until doubling of the baseline PSA, clinical or radiographic progression, or unacceptable toxic effects.

Main Outcome and Measure The primary end point was a confirmed 50% or higher decline in PSA from baseline (PSA50). Key secondary end points were outcomes by HRR alteration status, as well as safety and tolerability.

Results Of the 51 male patients enrolled (mean [SD] age, 63.8 [6.8] years), 13 participants (26%) had a PSA50 response, all within the HRR-positive group (13 of 27 participants [48%]). All 11 participants with BRCA2 alterations experienced a PSA50 response. Common adverse events were fatigue in 32 participants (63%), nausea in 28 (55%), and leukopenia in 22 (43%), and were consistent with known adverse effects of olaparib.

Conclusions and Relevance In this nonrandomized controlled trial, olaparib monotherapy led to high and durable PSA50 response rates in patients with BRCA2 alterations. Olaparib warrants further study as a treatment strategy for some patients with BCR prostate cancer but does not have sufficient activity in those without HRR alterations and should not be considered for those patients.

Trial Registration ClinicalTrials.gov Identifier: NCT03047135

Reproductive Health Oncology Prostate Cancer Urology Urologic Cancer Cancer Biomarkers Genetics and Genomics Targeted and Immune Therapy Clinical Pharmacy and Pharmacology Adverse Drug Events

Citation

Marshall CH, Teply BA, Lu J, et al. Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy: A Nonrandomized Controlled Trial. JAMA Oncol. 2024;10(10):1400–1408. doi:10.1001/jamaoncol.2024.3074

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