First genetically targeted treatment for metastatic prostate cancer that no longer responds to hormone therapy
Men with metastatic, hormone-resistant prostate cancer, who were treated based on the genetic makeup of their cancer, survived significantly longer than those treated with traditional hormone treatments, according to a large, international phase 3 clinical trial published in the New England Journal of Medicine and co-led by investigators from Northwestern Medicine, The Institute of Cancer Research in London and The Royal Marsden NHS Foundation Trust.
“Our results show genetically targeted treatment can extend the lives of patients with advanced prostate cancer that has progressed after several types of therapies, including hormone therapy,” said Maha Hussain, MBChB, the Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology, a Northwestern Medicine oncologist, and co-leader of the PROfound trial, which investigated the drug olaparib.
“We are now entering a new era of personalized care and precision medicine for metastatic prostate cancer. This will change clinical care for prostate cancer,” Hussain said.
Hussain is also deputy director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
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Olaparib, currently used to treat breast, ovarian and pancreatic cancer, was used successfully to treat prostate cancers with an inability to repair damaged DNA.
“This marks a significant advance for prostate cancer treatment, which has lagged behind other common cancers with regard to precision therapy, now the standard of care in many cancers including breast, ovarian, pancreatic and lung cancers,” Hussain said.
The trial treated men with metastatic prostate cancer that had progressed after several types of prior standard therapies, including hormone therapy.
The trial preselected patients who have genetic alterations in the genes that enable cells to repair themselves from damage. Those most commonly known are the BRACA 1, BRACA 2 and ATM genes, but there are several others. Patients were randomly assigned to receive olaparib, which has been used in other cancers with similar genetic alterations, or standard hormone therapy with either abiraterone and prednisone or enzalutamide.
There were two cohorts of patients based on their cancer genetic mutations. The median duration of overall survival in patients in cohort A with mutations on BRCA1, BRCA2 or ATM genes was 19.1 months with olaparib compared to 14.7 months with control therapy, a number considered clinically and statistically significant.
In cohort B patients (those with other genetic mutations), the median overall survival was 14.1 months with olaparib and 11.5 months with control therapy, but this was not statistically significant.
In 2020, there will be an estimated 191,930 new cases of prostate cancer and about 33,330 deaths from it. Prostate cancer continues to be the second leading cause of cancer death in men in the United States. In 2016, there were an estimated 3,100,000 men living with prostate cancer in the U.S.
The trial had previously reported a delay in disease progression for this group of men with DNA repair faults in their tumors – but these final published results offer a longer follow-up and conclusively demonstrate an improvement in survival for men who were given olaparib.
Olaparib blocks PARP, a protein that helps damaged cells repair themselves. Some cancer cells rely on PARP to keep their DNA healthy. When PARP is stopped from repairing DNA damage, the cancer cells die.
“We want to prevent those renegade cancer cells from repairing themselves,” Hussain said.
The study was funded by AstraZeneca and Merck & Co., which produces olaparib under the name Lynparza.
