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Results from a recent Phase II clinical trial conducted by Johns Hopkins Kimmel Cancer Center in association with the University of Nebraska Medical Center in Omaha, the Allegheny Health Network Cancer Institute in Pittsburgh and the Thomas Jefferson University Hospital in Philadelphia, found that Olaparib has the potential to treat biochemically recurrent prostate cancer without accompanying hormone therapy in men with gene mutations. Particularly, the results demonstrated efficiency in treating BRCA2 mutations.1
“This study is a breakthrough because it is the first trial to show that a non-hormonal drug can induce durable complete remissions in recurrent prostate cancer patients with BRCA2 mutations—one of the most aggressive subtypes of this disease,” said Emmanuel Antonarakis, MD, former Kimmel Cancer Center prostate cancer expert, co-leader of the study, in a news release. “It is a true paradigm shift, because now we can offer a non-hormonal precision therapy to these patients that is safe and effective while avoiding the side effects caused by hormonal deprivation.”
The clinical trial was a single-arm, nonrandomized controlled trial that enrolled 51 men with recurring prostate cancer post-prostatectomy, as indicated by rising PSA levels. The dosage level was 300 mg twice daily by mouth until doubling of the baseline prostate-specific antigen (PSA), clinical or radiographic progression, or unacceptable toxic effects. The primary endpoint of the trial was a confirmed 50% or higher decline in PSA from baseline, while secondary outcomes included key outcomes by homologous recombination repair (HRR) alterations, safety, and tolerability.86 percent of the trial participants had received radiotherapy after surgery.
Results found that Olaparib demonstrated significant efficacy in men with specific genetic mutations, particularly BRCA2, where all 11 patients with this mutation experienced a PSA reduction of 50% or more. Additionally, 26% of all enrolled patients experienced a PSA reduction of 50% or greater, all within the HRR-positive group. PSA progression-free survival was 22.1 months in biomarker-positive patients, compared to 12.8 months in biomarker-negative patients.1,2
Common adverse events (AEs) included fatigue, nausea, and leukopenia, all of which were consistent with previous studies and the known profile of Olaparib.2
According to the American Cancer Society, it is estimated that there will be 299,010 new cases of prostate cancer in the United States by the end of the year, with 35,250 deaths expected. Around one in eight men will be diagnosed with prostate cancer during their lifetime. It is rare in men under the age of 40, and in most cases, patients with prostate cancer are over the age of 65 years old. The average diagnosis age is 67 years old, and it is most common in African American men and Caribbean men of African ancestry.3
“Prostate cancer is the second-leading cause of cancer death in American men, behind only lung cancer,” reports the American Cancer Society. “About 1 in 44 men will die of prostate cancer. Prostate cancer can be a serious disease, but most men diagnosed with prostate cancer do not die from it. In fact, more than 3.3 million men in the United States who have been diagnosed with prostate cancer at some point are still alive today.”
According to the authors of the study, Olaparib has potential as a non-hormonal treatment option for patients with genetic susceptibilities such as BRCA2 mutations, avoiding the adverse effects associated with androgen deprivation therapy, including hot flashes and fatigue.1
References
1. Precision drug olaparib may be effective without hormone therapy for some men with biochemically recurrent prostate cancer. EurekAlert! August 22, 2024. Accessed August 30, 2024. https://www.eurekalert.org/news-releases/1055115
2. Olaparib Without Androgen Deprivation for High-Risk Biochemically Recurrent Prostate Cancer Following Prostatectomy. JAMA Network. August 22, 2024. Accessed August 30, 2024. https://jamanetwork.com/journals/jamaoncology/article-abstract/2822705
3. Key Statistics for Prostate Cancer. American Cancer Society. Accessed August 30, 2024. https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html#:~:text=stage%20prostate%20cancer.-,Risk%20of%20getting%20prostate%20cancer,Risk%20Factors%20for%20Prostate%20Cancer.