First trial shows benefit in genomic targeted prostate cancer treatment

• Link to: Northwestern Now Story

By Will Doss

For the first time, advanced prostate cancer has been treated based on the genomic makeup of the cancer, delaying progression for patients with metastatic castration-resistant prostate cancer, a deadly and treatment-resistant form of the disease.  

Published April 28 in the New England Journal of Medicine, the clinical trial represents a breakthrough in treating this cancer and for precision medicine more broadly, according to Northwestern Medicine oncologist Dr. Maha Hussain, the Genevieve E. Teuton Professor of Medicine and co-lead author of the study. 

“We have indeed entered a new era of personalized and precision medicine for metastatic castration-resistant prostate cancer, and I am confident more will be coming,” said Hussain, who is also deputy director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.  

In 2020, there will be an estimated 191,930 new cases of prostate cancer in the United States, with more than 33,000 deaths from the disease, according to the National Cancer Institute.  

In particular, metastatic castration-resistant prostate cancer, in which the cancer has spread beyond the prostate and grows despite hormone treatments, continues to be deadly despite advances in treatment, according to Hussain.  

This lethality is partly due to gene mutations in BRCA1, BRCA2 and other similar genes that help cells maintain stability of genetic material. Normally, these genes help repair DNA damage, but when they are mutated cells are not repaired correctly. 

These mutations complicate the biology of the cancer, but can also be exploited by drugs such as olaparib — a drug that blocks cell repair proteins and has been used in ovarian and breast cancers with similar repair mutations. 

“We want to prevent those renegade cancer cells from repairing themselves,” Hussain said.  

The current trial enrolled patients with one or more of these mutations who were randomized to receive either standard hormone therapy or olaparib. Patients in the olaparib cohort experienced delayed disease progression an average of seven months compared to three months for the standard treatment cohort.   

About 60 percent of men in the olaparib group showed no disease progression at six months, compared to 23 percent in the standard cohort.  The benefit was observed across the board, irrespective of the patient’s prior treatment, where the cancer had spread to (bone, liver or lymph nodes), the patient’s PSA (prostate-specific antigen) or age. 

The drug is currently under review by the Food and Drug Administration.

“The approach in the treatment of this disease to date has been a ‘one size fits all approach,’ yet different patients respond differently to the current standard of care treatments,” Hussain said. “Better personalization of therapy allows for maximizing the benefit to risk ratio.” 

This study was sponsored by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck.