New Drugs May Help Immune System Fight Cancer
Both studies, which are being presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago and also published in the New England Journal of Medicine on Saturday, explain that when two certain molecules are present, it renders the T-cell useless. T-cells hunt down cancer cells and destroy them. After a while, however, T-cells can start expressing a molecule called PD-1, which then can attract them to another molecule found on a tumor cell called PD-LI, explains Dr. Suzanne Topalian, lead author of one of the studies.
When these two molecules meet, it can render the army of T-cells useless. That’s because when the PD-1 and PD-L1 molecules connect, it “creates a protective shield that shields the tumor from immune attack … the T-cells will be turned off,” said Topalian, the director of the Melanoma Program at Hopkins’ Sidney Kimmel Comprehensive Cancer Center.
In the first study, researchers used an experimental drug, with the working name BMS-936558, which is an antibody that blocks the PD-1 molecule. “It functions to rescue exhausted T-cells and to enhance an anti-tumor immunity,” Topalian said.
Nearly 300 patients with advanced melanoma (a deadly form of skin cancer), colorectal cancer, non-small cell lung cancer, prostate cancer and kidney cancer participated in this phase 1 clinical trial, which is designed to test if a drug is safe. All of these patients had failed on at least one and up to five previous cancer treatments.
Patients were given this new drug once every two weeks for eight weeks. If after the first dose their cancer continued to grow or they got sicker, they didn’t continue with the trial. Fourteen percent of the trial participants had serious side effects and 5% of patients dropped out of the trial because of side effects.
Three patients died from complications of this treatment. Two lung cancer patients and one colon cancer patient developed severe lung inflammation called pneumonitis.
Topalian says in the course of the study, researchers learned how to better identify those who were at risk for side effects and also found better ways to detect problems early and treat them more effectively.
Of the remaining patients who were treated and had at least six months of follow-up, study results show the drug appears to work well in melanoma, lung and kidney cancer patients.
Twenty-six percent of the skin cancer either had their tumor completely or significantly shrink. Among the lung cancer patients, for which immunotherapy seemed elusive so far, 18% saw complete or partial regression of their tumors. Twenty-seven percent of kidney cancer patients saw their tumors shrink significantly.
The drug did not appear to help prostate or colon cancer patients.
Experts, including the study authors, are cautiously optimistic about the results, knowing that much larger studies need to be done to confirm the effectiveness of this new drug.
“This is eye-popping for renal (kidney) cancer,” says Dr. Nicholas Vogelzang, a prostate and kidney cancer specialist at the Comprehensive Cancer Centers of Nevada and spokesman for ASCO.
Dr. Mark Kris, a lung cancer expert at Memorial Sloan-Kettering Cancer Center in New York, who was involved in some of the research, says the approved lung cancer drugs given to patients who no longer respond to their first cancer treatment have a 7% response rate. “So if you see something that has a response rate of 20% or 30%, that is really different from what we’re used to seeing in that population.
“So I think that’s what got people excited.”
In the second trial, also headed by another Hopkins oncologist, Dr. Julie Brahmer, researchers studied 207 patients with non-small cell lung cancer, melanoma, kidney, breast, ovarian, gastric, pancreatic and colorectal cancers. Patients with lung, kidney, ovarian and skin cancer saw a benefit because their tumors shrank significantly — some even for more than a year after taking the experimental drug.
While neither trial shows whether patients will live longer because the research is so new, they both show that by shutting down the PD-1 and PD-L1 molecules, certain cancers may be stopped from getting worse — at least for some time.
“It’s exciting to see this degree of anti-tumor activity from a single agent among patients with a range of cancers that had progressed despite standard therapies,” Topalian said.
Moreover, they may have found a way to find out which patients may benefit from these treatments before giving it to them. By looking at the tumors of 42 patients before getting treatment, when they found if the PD-L1 molecule was present, the drug worked well in 36% of the patients. If that molecule wasn’t present, there was no response.
Larger studies are planned, and both studies were funded by grants from Bristol-Myers Squibb, the National Institutes of Health and the Melanoma Research Alliance.