Kim Sherman was in bad shape a year ago after a lemon-sized melanoma tumor in her pelvis stopped responding to standard targeted therapy. By late June 2013, the pain from the mass pressing on her hamstring became so bad she could hardly sleep, walk, or even sit down.
Then she joined a trial on an experimental drug from Bristol-Myers Squibb Co. designed to boost the immune system against her tumor when used in combination with the company's existing immune enhancing drug Yervoy. Within three weeks the pain started to subside, and within three months later the tumor disappeared. Her doctor at Yale Cancer Center in New Haven may stop therapy entirely in a few weeks, she said.
"I was ecstatic. I had the best possible result," said Sherman, a 48-year-old mother of three from Buchanan, New York. "This is a pretty remarkable drug combination."
At the American Society of Clinical Oncology meeting in Chicago, results like this are raising hopes that new immune system-boosting medicines can produce long survival in numerous advanced tumors, at least for those who respond to the drugs.
In Sherman's trial, 79 percent of an initial group of 53 patients who received the experimental medicine nivolumab combined with Yervoy were still alive after two years, a better result than is seen with existing drugs for advanced melanoma.
In another study of 411 advanced melanoma patients who got Merck & Co.'s drug, called MK-3475, 62 percent were alive 18 months after starting treatment, according to results being released at the meeting. Merck has already applied for U.S. Food and Drug Administration marketing approval based on the results, with a decision due in October.
"The difference with immune therapy is you are actually producing long term survival as opposed to extending someone's life a few months," said Steven O'Day, a medical oncologist and melanoma specialist at the Beverly Hills Cancer Center. The new results are "much better" than what is seen with approved melanoma drugs, he said.
Just a few years ago, immune boosting drugs were mostly known for their ability to help melanoma patients. Now testing is expanding rapidly to lung cancer, kidney cancer, and numerous other tumors types. Merck & Co., Bristol-Myers Squibb Co., AstraZeneca Plc, and Roche Holding AG are all racing to test the new class of immune therapy drugs in as broad an array of tumors as practical.
At the meeting in Chicago that promise was extended to several new types of malignancies.
Merck's MK-3475 was found to shrink tumors in 11 of 56 patients with head-and-neck cancer. In a second study presented to a packed auditorium on May 31, doctors revealed that 13 of 30 patients with advanced bladder cancer, whose tumors contained a certain immune protein, had major tumor shrinkage after being treated with Roche's drug MPDL3280A.
"I don't think there is a tumor type that is not going to respond to some form of immune therapy," said Padmanee Sharma, a genitourinary oncologist at the MD Anderson Cancer Center, who is involved in testing Bristol-Myers' drug in breast cancer, pancreatic cancer, gastric cancer and several other tumors.
For advanced bladder cancer, Roche's immune therapy treatment is the most promising new agent "in at least 25 years," said Nicholas Vogelzang, an oncologist at US Oncology in Las Vegas, who was involved in the Roche trial.
The theory behind the therapies is fairly simple. A protein called PD-1 acts as a switch to shut off the action of attack cells within the immune system that respond when the body is struck by a foreign invader. Some cancer cells have a unique ability to flick the off switch to disrupt attack by the immune system.
The drugs being developed work by either binding to the PD-1 protein to protect it from manipulation by tumor cells, or by hitting a related protein called PD-L1 that some tumor cells deploy to trigger the PD-1 switch.
While only a minority of patients on PD-1 experimental drugs respond to them, the difference between the immune therapy drugs and conventional cancer drugs is that the responses that do happen tend to be very long lasting, researchers at the conference said. By contrast, tumors often quickly grow resistant to existing drugs that that narrowly target one or two mutated proteins inside a tumor.
The new immune therapy drugs also have potential downsides. The PD-1 drugs can produce immune related side effects, such as lung inflammation.
Once immune system cells are generated against a tumor, versions of them remain in the body for the rest of someone's life, said James Allison, an immunologist at the MD Anderson Cancer Center in Houston said in an interview at the meeting. The immune system is also adaptable, and can react to changes in the tumor, he said.
Researchers at the meeting also reported data from a 951- patient study examining whether Bristol-Myers' Yervoy, now approved for advanced melanoma, could help prevent relapse in patients with earlier-stage melanoma at high risk of recurring.
While the trial found that the drug reduced the risk of relapse by 25 percent over a 2.7 year period compared to a placebo, patients on Yervoy had more side effects. More than half of patients on Yervoy discontinued the drug due to the side effects, and five patients died of drug-related toxicity.
The result "raises as many questions as it answers," said Jeffery Weber, an oncologist at the H. Lee Moffitt Cancer Center in Tampa, Florida.
Among the issues is the cost of the potential new regimen, Weber said. Because the new trial used a much higher dose than that currently approved for Yervoy and treats patients for a longer period, the full regimen used in the trial would cost as much as $1.5 million for a single patient, he estimated.
In an e-mail, Bristol-Myers Squibb spokeswoman Sarah Koenig said the company is "in process of evaluating options based on these results and it is premature to speculate on our regulatory plans."
Bristol-Myers is "sensitive to concerns about the rising costs of health care, including pharmaceuticals" and is "actively evaluating ways to address other Yervoy dosing regimens being studied" to enable access for patients in need, Koenig said.
To contact the reporter on this story: Robert Langreth in New York at rlangrethbloomberg.net To contact the editors responsible for this story: Reg Gale at rgale5bloomberg.net Angela Zimm