“Hormone therapy, which is what we’ve been offering patients for 30 years, has not improved survival and neither has anything else.” That is how Dr. Stephen Freedland of Cedars-Sinai described the state of care for men whose prostate cancer comes back after surgery or radiation. A new trial, he said, changes the picture.
The study tested enzalutamide, an existing cancer drug, alongside standard hormone therapy. Men who received both lived longer than those in the comparison groups. After eight years of follow-up, the combination carried a 40.3% lower risk of death, Freedland said. Results appeared in The New England Journal of Medicine and were presented on Oct. 19 at the European Society for Medical Oncology Congress in Berlin.
Who was in the trial
More than 1,000 men took part, drawn from 244 medical centers in 17 countries. Every one had high-risk biochemically recurrent prostate cancer. In this condition, levels of prostate specific antigen (PSA), a protein doctors use to track the disease, climb quickly after treatment. A steep rise often means the cancer is likely to return and spread, frequently to the bones or spine.
Participants were assigned at random to hormone therapy alone, enzalutamide alone, or the two together.
“We know these patients are at high risk of developing metastatic disease and dying of their cancer unless we offer a meaningful treatment option,” said Freedland, who directs the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer and is co-principal investigator.
Guidelines may follow
Enzalutamide is already approved by the Food and Drug Administration and appears in National Comprehensive Cancer Network guidelines, based on earlier work by the same team. Freedland said the new data will probably strengthen those recommendations and make the pairing the standard of care for this group of patients.
Dr. Hyung Kim, chair of urology at Cedars-Sinai, said the analysis “will change how we take care of our patients.” Dr. Robert Figlin, interim director of Cedars-Sinai Cancer, called the trial an example of the translational work done by the center’s physician-scientists.
Pfizer Inc. and Astellas Pharma Inc., which co-developed enzalutamide, sponsored the study. Freedland reports consulting for Astellas, Pfizer and several other drugmakers.
A separate lab finding on resistant tumors
Elsewhere, University of Michigan researchers reported early work on tumors that outlast standard treatment. About one in eight men will be diagnosed with prostate cancer, and in the United States it is the second leading cause of cancer-related death among men. Androgen receptor inhibitors help at first, but nearly all patients eventually develop resistance.
Some resistant tumors survive by changing cellular identity, a process called transdifferentiation. The Michigan team, publishing in JCI Insight, paired two drug classes: BET bromodomain inhibitors, which slowed growth in cell lines but did not kill the cells, and DNMT inhibitors, which can switch silenced genes back on. Together they suppressed growth better than either alone, and the effect held in tumors implanted in mice.
“It is also promising that we saw a significant reduction in tumor growth even at doses far lower than the recommended dose, and this drug combination was well tolerated by the mice,” said Will Storck, a research lab specialist. Joshi Alumkal, who led the work, said the group now wants biomarkers that show which patients would benefit, and hopes to plan clinical trials.
Sources
- This powerful drug combo cuts prostate cancer deaths by 40%
- Scientists find a new weakness in treatment-resistant prostate cancer
