Olaparib monotherapy ‘true paradigm shift’ in biochemically recurrent prostate cancer
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Key takeaways:
- All men with BRCA2 mutations treated with olaparib monotherapy achieved at least a 50% decline in PSA.
- The study represents a “paradigm shift” in treatment for this population, researchers concluded.
Olaparib monotherapy may be an effective treatment option for certain men with biochemically recurrent prostate cancer, according to results of a nonrandomized phase 2 trial.
The drug exhibited particularly strong activity among men who had BRCA2 mutations.
“This study is a breakthrough because it is the first trial to show that a nonhormonal drug can induce durable complete remissions [among men with prostate cancer] with BRCA2 mutations — one of the most aggressive subtypes of this disease,” Emmanuel Antonarakis, MD, associate director of translational research at University of Minnesota Masonic Cancer Center, said in a press release. “It is a true paradigm shift, because now we can offer a nonhormonal precision therapy to these patients that is safe and effective while avoiding the side effects caused by hormonal deprivation.”
Olaparib (Lynparza; AstraZeneca, Merck) — a poly(ADP)-ribose polymerase (PARP) inhibitor — is approved in the United States for multiple oncology indications.
The agent has shown benefit in combination with hormonal therapies among men with metastatic prostate cancer who have homologous recombination repair alterations; however, its potential efficacy as monotherapy — without androgen deprivation therapy — has not been explored.
Antonarakis and colleagues conducted a single-arm phase 2 study to evaluate olaparib monotherapy for 51 men (mean age, 63.8 years) with high-risk biochemically recurrent prostate cancer following radical prostatectomy.
Eligible men had a PSA doubling time of 6 months or less, an absolute PSA of at least 1 ng/mL, and a testosterone level of at least 150 ng/dL.
Twenty-seven men had homologous recombination repair (HRR)-positive disease and 11 had BRCA2 mutations.
Men received 300 mg olaparib orally twice daily. Treatment continued until baseline PSA doubling, clinical or radiographic progression, or unacceptable toxicity.
A confirmed 50% or greater decline in PSA from baseline served as the primary endpoint. Key secondary endpoints included outcomes by homologous recombination repair alteration status, safety and tolerability.
Thirteen men (26%) — all of whom had HRR-positive disease — achieved 50% or greater decline in PSA from baseline. All 11 men with BRCA2 mutations achieved this outcome.
Olaparib exhibited a safety profile consistent with prior reports. The most common adverse events included fatigue (63%), nausea (55%) and leukopenia (43%).
Researchers acknowledged study limitations, including the small sample size, the lack of a control group and a higher prevalence of HRR alterations than typically observed among men with biochemically recurrent prostate cancer.
References:
- Marshall CH, et al. JAMA Oncol. 2024;doi:10.1001/jamaoncol.2024.3074.
- Precision drug olaparib may be effective without hormone therapy for some men with biochemically recurrent prostate cancer (press release). Available at: https://www.hopkinsmedicine.org/news/newsroom/news-releases/2024/08/precision-drug-olaparib-may-be-effective-without-hormone-therapy-for-some-men-with-biochemically-recurrent-prostate-cancer. Published Aug. 22,, 2024. Accessed Aug. 22, 204.
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Marshall CH, et al. JAMA Oncol. 2024;doi:10.1001/jamaoncol.2024.3074.
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