Will cancer immune therapy work for me?
Predicting who benefits
SAN DIEGO, Sept 20, (AP): Dennis Lyon was a genetic train wreck. Cancer was ravaging his liver, lungs, bones and brain, and tests showed so many tumor mutations that drugs targeting one or two wouldn’t do much good. It seemed like very bad news, yet his doctors were encouraged.
The reason: People with the most messed-up genes often are the ones who do best on treatments that enlist the immune system.
“These are the patients we used to be very depressed about”, thinking they couldn’t be helped, said Dr Razelle Kurzrock at the University of California, San Diego. “Now when we see those types of patients, we’re really excited”, because there are so many ways for the immune system to recognize the cancer cells as abnormal.
Immunotherapy is the hottest thing in cancer care. Drugs called checkpoint inhibitors can vanquish some advanced cancers by removing a chemical cloak that hides them from the immune system. Former president Jimmy Carter got one at age 91 for skin cancer that spread to his brain, and now is in remission.
But they’re expensive, have side effects, and work for only about one-quarter of patients — as few as 5 percent with colon cancer and as many as half with the skin cancer, melanoma. Sometimes the benefits are brief.
Backfire
Worst of all: For a small number of unlucky folks, treatment can backfire. Their cancer grows exponentially after getting a checkpoint drug.
“We’re going to have to figure out not only who to treat with immunotherapy but who not to treat”, Kurzrock said.
Gene tests are starting to help sort that out. But for patients, the big question is “Will it work for me?”
The first step is testing for a protein called PD-L1 that’s often involved in forming that chemical cloak. Some checkpoint drugs target this or a related protein, so people with a lot of it should respond to treatment.
That was the hope when Diane Tippett showed up last October at Georgetown Lombardi Comprehensive Cancer Center with a salivary gland cancer that had spread to her liver and lungs.
“Five years ago, I probably would have thrown up my hands and given her standard chemo”, said the center’s director, Dr Louis Weiner.
Instead, he ordered tests that showed Tippett had a PD-L1 mutation, meaning her cancer made a lot of it. He started the 49-year-old Leonardtown, Maryland, woman on a checkpoint drug, Opdivo, and told her to come back in a few months.
“Quite honestly, I didn’t know if I’d ever see her again”, he said.
Now, Tippett’s lung tumors are gone. Her liver tumor shrank 50 percent and is stable. She got married in July and says she feels great.
“I don’t feel any different than you do. I’m not tired, I’ve got all my hair”, she said. “I want more people to know about it and to ask their doctors about it”, she said of immunotherapy and the testing that led her to it.
Benefit
That protein isn’t a very reliable predictor, though. Some people with a lot of it don’t benefit from the drugs and the opposite also is true. There are other checkpoints besides that one, too.
Researchers increasingly are focusing on something else Tippett had: a high number of flawed genes. It’s a sign that tumors have been evolving over time and are hard to treat with drugs that target a single gene. It sometimes accompanies two other DNA problems that some checkpoint drugs already are approved to treat.
Lyon, the San Diego man, had nearly two dozen different mutations after his skin cancer spread widely. In October 2015, he started on Opdivo and was in near-complete remission within two months. Recent tests showed no active cancer in his spine and lungs, and doctors think small spots in his brain and liver may be scar tissue, though they can’t know for sure. A test for tumor DNA in his blood found none.
“It would appear my cancer is all dead”, he said, and called it “nothing short of miraculous” that gene tests led to successful treatment after years of trial and error. “I’m so grateful. No one’s lucky that gets cancer but I may be in an era where there’s a way through this tunnel”.