Olaparib may be sufficient for PSA recurrent prostate cancer among men with BRCA2 alterations

CANCER DIGEST – Aug. 24, 2024 – Men with mutations in a certain gene and whose prostate cancer is recurring as judged by a rising PSA, may be treated with the anti-cancer drug olaparib (Lynparza®) alone without additional hormone therapy a new small study shows.

Led by Cathy Handy Marshall, MD, MPH, of Johns Hopkins Kimmel Cancer Center, the study involved 51 prostate cancer patients who were experiencing signs of rising prostate specific antigen (PSA) after surgery to remove their prostates. The study results appear  in the Aug. 22, 2024 JAMA Oncology.

Of the 51 patients, 27 had some genetic marker indicating their cancers would respond to olaparib, 13 of them had a decrease of 50 percent or more in their PSA levels following olaparib treatment, indicating their cancers were subsiding, and 11 of those had mutations in the BRCA2 gene.

The median time the men whose cancer responded to olaparib was 19.3 months overall and 22.1 months for the 27 with the genetic markers that respond to the drug. That compared to 12.8 months of PSA progression-free survival for the men who did not have the genetic markers. 

The median survival time from treatment to detection of cancer spread was 32.9 months overall and 41.9 months in the biomarker-positive subset, compared with 16.9 months in the biomarker-negative subset. The median time before additional anti-cancer therapy was deemed necessary was 15.4 months overall and 22.7 months in bio-marker positive group compared to 2.4 months in the biomarker negative group.

Most men with localized prostate cancer that has not spread to other tissues are cured with surgery of radiation therapy, but up to 40 percent are determined to have recurrence based on a rising PSA after therapy. Such men are commonly treated with hormone deprivation therapy, which has side effects such as hot flashes, fatigue, or weight gain.

Olaparib is a targeted cancer drug that is FDA approved for the treatment of ovarian and other cancers of the female reproductive system in addition to prostate cancer.

The most common side effects were fatigue, nausea and leukopenia or diminished infection-fighting white blood cell counts.

“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,” Emmanuel Antonarakis, M.D., said in a press release. He is co-lead investigator on the study and associate director of translational research at the University of Minnesota Masonic Cancer Center. “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 study was a collaboration between Johns Hopkins, University of Nebraska, Allegheny Health Network Cancer Institute, Thomas Jefferson University Hospital, Veracity of San Francisco and the University of Minnesota Masonic Cancer Center. The study was funded by AstraZeneca, Foundation Medicine, and Veracity.

Resouces: Johns Hopkins Medicine press release and JAMA Oncology.