Personal cancer immunotherapies (PCIs) rebuke a decades-old misconception, says Matthew Galsky MD, director of genitourinary medical oncology at Tisch Cancer Institute at Mount Sinai in New York.
The son of a biologist and a teacher, Galsky graduated from Syracuse in 1994 and went to medical school at Tufts. He chose to work on bladder cancer for his fellowship at Memorial Sloan-Kettering Cancer Center because, compared to lung and breast cancer, bladder cancer was a neglected field — with a dearth of specialists and no new treatments in 30 years. “Scientists were making exciting discoveries about the molecular nature of cancer, and I wanted to apply science to medicine,” says Galsky.
The misconception: that cancer patients have dysfunctional immune systems. “Now we know,” says Galsky, “based on what has happened with these medications, that there is nothing inherently wrong with the immune system.”
However, in some patients, the immune system’s healing efforts are stymied if the ligand PD-L1 (a signal-triggering protein molecule) binds to its receptor, PD-1. PD-L1 may disguise and shield the tumor from the helpful ministrations of the immune system.
Two different proteins are interacting, Galsky explains, comparing PD-1 to the “lock” and PD-L1 to the “key.” Some companies are developing drugs to block the receptor and some to block the ligand.
Bristol-Myers Squibb is running direct-to-consumer television ads for Opdivo (nivolumab), which works on the “lock,” the receptor; it treats some kinds of lung cancer and melanomas, and on November 23 the FDA approved it for kidney cancer. Merck’s Keytruda, for Jimmy Carter, also works on PD-1.
Atezolizumab works on “the key,” the ligand PD-L1, and it is being used in nearly a dozen clinical studies of lung, kidney, breast, and bladder cancer. The atezolizumab therapy Newton gets, as yet unnamed, is made by Genentech. It received Breakthrough Therapy Designation from the FDA just before Newton entered the Phase II clinical trial (IMvigor210) and might get approved (and named) as early as next year.
In Newton’s trial, everyone received the drug, but researchers were not told which patients had high levels of the protein PD-L1. The “personalized” part of Personalized Cancer Immunotherapy is that the researchers hope to match which drugs to prescribe for which levels of the protein. The results: of the 311 patients who had had chemo, 100 showed medium or high levels of the protein PD-L1 and atezolizumab improved the outcomes for 27 of them.
Galsky suspects Newton had a high level of the protein but, as he says, “what matters is that he responded. We know that a large proportion of patients do not respond to these medicines, but when they do, they respond quite well.”
Immunotherapies represent just one of the exciting new cancer therapies under development. Gene-based therapies also hold great promise. But for Galsky, PCIs will have the broadest impact of any drugs that have been introduced on his watch. “PCIs will not only change the way we treat bladder cancer, but also the way we treat subsets of patients with all types of cancer,” says Galsky. “Particularly for those with metastatic cancer, their response can last a very long time.”
What does “very long time” mean? “We don’t know yet,” Galsky says.