Ovarian Cancer Drug Shows Promise With Tough-to-Treat Prostate Tumors

In small study, olaparib targeted gene mutation in men who had failed other therapy, researchers report

Wednesday, October 28, 2015

WEDNESDAY, Oct. 28, 2015 (HealthDay News) -- In a small trial, a drug designed to fight inherited ovarian cancers in women appeared to help some men with advanced prostate cancer.

Lynparza (olaparib) targets mutations that are found in about 30 percent of men with prostate cancer. But, it also seemed to benefit men whose tumors have acquired defects in DNA repair, the British researchers said.

"This is the first time a drug with potential to be used for treating advanced prostate cancer is associated with a clear genetic signature, permitting us to predict who is likely to benefit from the therapy," said lead researcher Dr. Joaquin Mateo, a medical oncologist at the Institute of Cancer Research in London.

The researchers are now conducting a second trial to confirm the results, he said.

"We believe this is the most relevant step towards delivering personalized management, guided by the characteristics of each tumor for patients with advanced prostate cancer," Mateo said.

Olaparib, a type of drug called a PARP inhibitor, was approved last year by the U.S. Food and Drug Administration for women with ovarian cancer that is associated with defective BRCA genes. But, it has not been approved to treat prostate cancer, Mateo said.

"We have shown the potential for olaparib to help a group of patients with advanced prostate cancer by choosing the best treatment for each patient, maximizing the chances of helping and avoiding unnecessary treatments to patients who are unlikely to benefit," he said.

This advance has been made, in part, by the ability to test patients' DNA to find those who will benefit most from the drug, he said.

"New DNA-sequencing techniques, which are cheaper and more accessible than they were a few years ago, can provide more precise care to advanced prostate cancer patients," Mateo said.

The report was published Oct. 29 in the New England Journal of Medicine.

For the study, 49 men with advanced prostate cancer who were no longer responding to standard therapies received olaparib. Of these, 16 (33 percent) responded to the drug.

"We observed that about a third of the patients had a response in the tumor, normally lasting over six months and many times over a year," Mateo said.

Most interesting was that almost all patients benefiting from the therapy had something in common, he said. Specifically, their tumors had genetic switches in one or more genes involved in repairing the damage to DNA, Mateo said.

Only two of the 33 patients who did not respond to the drug had these genetic changes, he said. "Therefore, we believe we have found a way to predict which patients are likely to respond to this new therapy," Mateo said.

In the men who responded to the drug, olaparib stopped prostate cancer growth and caused lasting drops in prostate-specific antigen (PSA) levels. The drug also caused drops in tumor cells in the blood and led to shrinkage of tumors seen on CT and MRI scans, the researchers found.

Dr. Anthony D'Amico, chief of radiation oncology at Brigham and Women's Hospital in Boston, was not involved with the study, but reviewed its findings. "This is an important first step towards precision medicine, in which you can target a particular gene mutation with a drug," he said.

However, how effective the drug is in prolonging life over the long term isn't yet known, he said, although it's promising that the men who tried and failed other advanced treatments responded to the drug.

"I am encouraged by the response rate," D'Amico said. "But response doesn't necessarily mean living longer."

SOURCES: Joaquin Mateo, M.D., medical oncologist, Institute of Cancer Research, London, England; Anthony D'Amico, M.D., Ph.D., chief, radiation oncology, Brigham and Women's Hospital, Boston, Mass.; Oct. 29, 2015, New England Journal of Medicine

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