Immunotherapy effective against ‘untreatable’ prostate cancer
A major trial has demonstrated, for the very first time, that the immunotherapy drug pembrolizumab (Keytruda) is effective in treating advanced prostate cancer that did not respond to other treatments.
Immunotherapy is a form of treatment that can enhance one’s immune system in the fight against cancer. Checkpoint inhibitors, in particular, are a type of drug that works by taking the “brakes” off of the immune system, releasing its T cells to attack cancer cells.
Previous research has shown immunotherapy to be particularly effective in treating cancers that have high levels of acquired genetic mutations, such as melanoma, lung cancer, and bladder cancer. In prostate cancer, however, previous trials have suggested that immunotherapy does not work. But a new study examines the genetic makeup of prostate cancer tumors and shows that this approach singles out a group of patients for which the therapy might actually work. In fact, the trial shows that 1 in 10 men who were failed by all other types of treatment have benefited from the checkpoint inhibitor drug pembrolizumab, and that for many of these patients, the benefits are still showing after a year.
“This is exciting because any time we can extend the survival rate of a patient, we are extending the time his family and friends get to be with him. And it’s not just an extension of time. It’s also a very good quality of life thanks to minimal side effects typical of immunotherapy,” said David M. Waterhouse, MD, MPH, co-director of research at OHC.
The trial was carried out by researchers at the Institute of Cancer Research in collaboration with those at the Royal Marsden NHS Foundation Trust — both in London, England. The results were presented at the annual meeting of the American Society of Clinical Oncology, held in Chicago, IL.
During this trial, the researchers administered pembrolizumab to 258 men with advanced prostate cancer. Of these, 38 percent survived for a year, and 11 percent are still taking the drug a year after the trial ended, with no signs of their cancer advancing. Though this percentage may seem small, the response rate was much higher in people whose tumors had mutations in their DNA-repairing genes, such as BRCA mutations.
Although the researchers do not yet know why this subset of patients benefited so much more from immunotherapy, they do have a hypothesis. In fact, they believe that these highly mutated cancer cells might be easier to identify and target by the immune system because they look so different from normal cells.
In future trials, the scientists are planning to test the effect of the checkpoint inhibitor in men with DNA-repairing gene mutations. For now, the scientists compared the effects of pembrolizumab in patients whose prostate tumors were covered in a protein called PD-L1 with those who did not have this protein. The researchers found that examining PD-L1 levels was not enough to predict which patients would respond to immunotherapy; instead, they found clues that another protein called PD-L2 may be a better predictor.
“I’m not surprised by these findings because the application of immunotherapy for treating cancer is exploding,” Dr. Waterhouse added. “As we learn more about the immune system and why it won’t attack cancer cells, we can use these findings to modify these new treatments so they can be used to fight more cancers. But, we still have much to learn about which populations of patients might benefit the most. Immune therapies are still in their infancies.”