Penn trial suggests ‘triple threat’ for melanoma patients could be effective

Results from a clinical trial published online in the journal Nature Monday introduce a new “triple threat” combination that could be effective in treating melanoma that’s spread throughout a patient’s body.

A new class of cancer drugs called checkpoint inhibitors can clear out metastatic cancer, but they work on only about one in five patients.

In a small trial of metastatic melanoma patients, University of Pennsylvania researchers used targeted radiation in combination with the checkpoint inhibitor ipilimumab to see if they could increase that drug’s efficacy.

One of the paper’s authors, Dr. Lynn Schuchter, an oncologist at Penn’s Abramson Cancer Center, said the goal was to see if radiating just one tumor would help the body’s immune system recognize other, camouflaged tumors elsewhere in the body.

“When we radiate the tumor, we kill some melanoma cells, (and) it releases antigen in a different way,” Schuchter said. “That is presented to the immune system, and now a more effective, revved-up T-cell can be more effectively steered to the cancer.”

In the trial, non-radiated tumors shrank significantly in only four out of 22 trial participants, or 18 percent.

However, when the research team went back to the lab and added a third immunotherapy drug to treatment in mice, tumors disappeared in between 60 and 80 percent of the animals.

Johns Hopkins oncologist and immunotherapy expert Charles Drake said going back to the lab mice is what makes this paper significant, though the small human trials did not show significant patient benefit in adding radiation to ipilimumab.

“It’s important because that leads to a path going forward, and that is to combine radiation therapy with both CTLA-4 blockade and PD-1 blockade,” Drake said.

Those “blockades” are the two immune therapy drugs the Penn researchers used in mice. A clinical trial to see if they will work in humans is currently in development.