Interim results from a clinical trial conducted by researchers in the Netherlands and Australia suggest that some melanoma patients may need far less immunotherapy than they’re currently prescribed.
The Phase 3 study asked when and how much immunotherapy certain melanoma patients should receive with surgery, an ongoing question in the field. In the 400-patient study, one group got standard treatment: surgery to remove the enlarged lymph node and then one year of immunotherapy. The other group had two rounds of the immunotherapy drugs Opdivo plus Yervoy — a more intensive, but shorter initial regimen — and then surgery.
The results could meaningfully change how oncologists treat those patients, who have what’s known as macroscopic stage 3 disease — meaning that their melanoma has traveled to a local lymph node, which became enlarged.
In the group that got the shorter, more intense immunotherapy before surgery, 58% of them saw a major response, meaning at least 90% of their tumor died, and they didn’t receive further immunotherapy after surgery.
At 10 months, the pre-surgery immunotherapy regimen cut the risk of cancer returning, progression, complications or death by 68%, compared with patients getting immunotherapy after surgery. At 12 months, an estimated 84% of patients who received immunotherapy before surgery experienced no such events compared to 57% of the patients who only received immunotherapy after surgery.
Lynn Schuchter“This is going to be groundbreaking,” said Charles Lance Cowey of Texas Oncology in Dallas, who was not involved with the study.
During Sunday’s presentation, researchers noted that the results were from an interim readout and the study still needs longer follow-up. And it’s a subgroup that doesn’t make up all stage 3 patients, said Cowey, but he did note that it was a “big” minority of the stage.
But the results, which were presented Sunday at the American Society of Clinical Oncology’s annual meeting, are likely to have an impact on the field.
“When I go home on Tuesday, I have clinic Thursday. I would consider [this treatment] now for my patients,” said Lynn Schuchter, director of Penn Medicine’s Tara Miller Melanoma Center in Philadelphia. She was not involved with the study.
New questions about immunotherapy
They’re also likely to deepen the debate among oncologists about when it’s best to give immunotherapy around surgery and how much is enough.
“There is something probably about the biology when you’re giving neoadjuvant immunotherapy that having tumor present and tumor antigens present helps stimulate a more effective immune response,” Schuchter said. Neoadjuvant refers to giving therapy before surgery.
One patient in the adjuvant arm of the study died from pneumonitis or lung inflammation. Overall, patients who received the dual immunotherapies experienced a greater percentage of serious side effects related to treatment.
Christian BlankTo Christian Blank, the Netherlands Cancer Institute researcher who led the study, the findings mean that ongoing adjuvant studies in melanoma that include similar stage 3 patients may need to reconsider their designs. “After NADINA, it’s unethical to include a patient into an adjuvant arm,” he said. “You need to now use a neoadjuvant comparator.”
“This will actually disrupt a lot of people’s plans for the future, like Moderna with the neo-antigen approach,” said Igor Puzanov, SVP of clinical investigation at the Roswell Park Comprehensive Cancer Center in Buffalo, referring to Merck and Moderna’s development of a cancer vaccine. Puzanov was not involved in either study.
Merck and Moderna are currently running a Phase 3 melanoma study of the vaccines, which includes patients whose disease are in stages 2 to 4. Macroscopic stage 3 patients make up a small portion. In that study, patients either received Moderna’s cancer vaccine plus Keytruda after surgery or a placebo and Keytruda after surgery. Merck responded that it had no comment, and Moderna did not respond to a request for comment.