Breakthrough Prostate Cancer Therapy Targets Genes to Delay Progression
Published December 2019
Medication Offers Individualized Treatment
This article was originally published in Northwestern Medicine Feinberg School of Medicine News Center. It has been modified for Northwestern Medicine’s content hub, HealthBeat.
Roughly, men have an 11 percent (one in nine) risk of being diagnosed with prostate cancer in their lifetime. The risk for prostate cancer is between 30 percent and 60 percent for men with a BRCA2 gene mutation, and between 10 percent and 30 percent for men with a BRCA1 gene mutation.
Results from a phase 3 clinical trial may transform treatment for men who have been diagnosed with metastatic (advanced) castrate-resistant prostate cancer (MCRPC) who also have mutations in their genes like BRCA1, BRCA2 and others.
Olaparib, the medication studied in the trial, is the first-ever treatment for MCRPC based on the genetic composition of the tumor to show benefit, offering an unprecedented ability to customize treatment for those with genetic mutations.
“Treatments for metastatic, hormone/castration-resistant prostate cancer have continued to use ‘one-size-fits-all’ approaches, overlooking the genomic make-up of the tumor,” says clinical trial principal co-investigator Maha Hussain, MD, FACP, FASCO, medical oncologist at Northwestern Medicine and deputy director of Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “I am confident we are now entering a new era of personalized care and precision medicine for metastatic prostate cancer.”
How olaparib works
Cancer cells grow — wildly. Some rely on a protein called poly-ADP ribose polymerase (PARP) to help them repair their DNA to keep growing. Olaparib blocks PARP, “preventing those renegade cancer cells from repairing themselves,” says Dr. Hussain. They eventually die.
In this clinical trial, olaparib nearly doubled the time patients with MCRPC and genetic mutations had without any disease progression. That’s 7.4 months for the patients treated with olaparib who have BRCA1, BRCA2 and ATM mutations, compared to 3.6 months for the control group of patients treated with standard hormone therapy for prostate cancer. As soon as men in the control group showed disease progression, they were given the medication.
Six months after treatment, about 60 percent of the men receiving olaparib showed no disease progression. In the control group, 23 percent of men showed no disease progression. After one year, about three times as many men given olaparib showed no disease progression compared to the control group.
Slowed prostate cancer progression with olaparib occurred regardless of the location of the cancer, prior treatment, if and where the cancer had spread, the patient’s PSA (prostate-specific antigen) level and age.
Another benefit is pain management. “When prostate cancer spreads to the bone, it can cause significant pain. When patients received olaparib, they had a longer time before pain occurred or progressed,” says Dr. Hussain. “Pain destroys quality of life.”
The bottom line? Early data indicate that the number of patients with advanced MCRPC who are alive after six, 12 and 18 months of treatment is higher among those who received olaparib compared to those who did not.
|One-year survival rate for men with MCRPC
(Please note: Survival data is not mature yet.)
|With olaparib||Without olaparib|
|73 percent||56.94 percent|
Olaparib for treatment of metastatic, hormone-resistant prostate cancer is currently undergoing expedited review by the Food and Drug Administration (FDA).
Olaparib is currently approved by the FDA for treatment of breast and ovarian cancer for people with BRCA1 and BRCA2 gene mutations.
Olaparib is a potential tool in a multi-targeted treatment strategy for men with MCRPC who have genetic mutations. It shows promise of delaying disease progression, reducing pain, and lessening the damaging effects that prostate cancer and its treatments may have on the body.
“Any time you have an effective treatment that can add value in terms of quality and quantity of life, a cure for cancer becomes even more possible,” says Dr. Hussain.