First Trial Shows Benefit for Genomically Targeted Prostate Cancer Treatment

by

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 in the New England Journal of Medicine, the clinical trial represents a breakthrough in treating this notoriously deadly cancer, and for precision medicine more broadly, according to Maha Hussain, MBChB, the Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology and senior 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 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, where the cancer has spread beyond the prostate and grows despite hormone treatments, continues to be deadly despite advances in treatment, according to Hussain.

Maha Hussain, MBChB, the Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology, was senior author of the study published in the New England Journal of Medicine.

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, and they were randomized to receive either standard hormone therapy or olaparib. Patients in the olaparib cohort experienced delayed disease progression on average: seven months compared to just three months for the standard treatment cohort.

Further, 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 and if approved, it would make available a new genomically targeted treatment that could provide benefit to prostate cancer patients, according to Hussain.

“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.

Listen Up: Hear an interview with Hussain in Feinberg’s Breakthroughs podcast series here.