FDA’s Approval of New Keytruda Indication Yields Fresh Treatment Option for ‘Gigantic Group of Patients’ With Melanoma

The Food and Drug Administration’s (FDA) recent approval of a new indication of Keytruda (pembrolizumab) to be given following surgical resection of stage 2b, 2c or 3 melanoma provides a significant group of patients a new treatment option that they previously didn’t have access to, according to an expert

The FDA in 2019 gave Keytruda the OK to treat patients with resected, high-risk, stage 3 melanoma. However, the issue there, according to Dr. Jason Luke, is how “high-risk” has been historically classified.

“There has been a misnomer in the field about what constitutes high risk,” Luke, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center in Pittsburgh, said in an interview with CURE®. “Historically, in melanoma, we deemed high-risk disease to be that which involved the lymph nodes after surgery, and that's why we originally did completion lymph node dissection and sentinel lymph node biopsies.”

Of note, Luke explained that previous studies have shown that patients who have deep primary lesions — meaning that the tumor is at least 2 millimeters thick with or without a breakdown of skin on top of the melanoma — have similar melanoma-specific survival outcomes to those considered high-risk, stage 3.

In other words, he said, death from melanoma has historically been similar between patients with deep lesions without disease present in their lymph nodes and those with high-risk disease and traces of the cancer in their lymph nodes.

“And yet, adjuvant anti-PD-1 immunotherapy was only approved for the lymph node-positive patients,” he said. “So these patients (stage 2b and 2c) didn't have access to treatment, even though their risk was the same as those who did. And that didn’t really make sense.”

As a result, Luke and colleagues initiated the global phase 3 KEYNOTE-716 trial to assess the safety and efficacy of Keytruda compared with placebo following resection in those patients who were not included in the initial approval in 2019.

Interim Analysis of KEYNOTE-716 Leads to Approval

The agency based its decision to approve Keytruda for children and adults over the age of 12 who have stage 2b, 2c or 3 melanoma that was fully resected based on data from the trial. At the first analysis, which the FDA used to determine its decision, treatment with Keytruda resulted in a 35% reduction in the risk of disease recurrence compared with placebo. Moreover, Luke told CURE® that since the initial analysis, an additional six months of follow-up data have shown the benefit has increased to a 39% reduction.

“That difference in recurrences actually translated to a reduction in metastatic recurrences (to the liver and other nearby organs) by 50%,” Luke, who was a study author on the KEYNOTE-716 trial, said. “We fully believe that as the trial matures further, we're going to see that the benefit actually increases over time … we fully expect that the benefit to (Keytruda) in the stage 2 b/c population will be the same as what it is in stage 3.”

‘There’s an Option to Reduce the Risk’

The results from KEYNOTE-716, along with this recent FDA approval, are significant for the overall melanoma patient population, according to Luke.

“There was this gigantic group of patients who were at similar risk but didn’t have a treatment option,” he said in the interview. “And that’s been fixed by this trial.”

Luke also explained how this outcome may be viewed by patients on an individual level.

“We come back to that risk of recurrence,” he said. “What we can say based on the trial now, is that there’s at least a 39% reduction in the likelihood that your melanoma would come back after it was resected.”

The question, however, is if the disease returns, can it just be resected again and then administer the immunotherapy later.

“The answer to that is, maybe,” he said. “That's where joint decision making with your doctor really makes a big difference because you can argue that well, on average, this might happen. But each person is not an average. And so each person will take their risk and what it means to them to have cancer and apply that differently in their lives.”

For instance, some patients are willing to try anything to ensure that there are no traces of the disease or chances of it recurring. Whereas, Luke noted, some patients will weigh the risks and benefits of immunotherapy and decide to hold off on receiving additional treatment.

Overall, he mentioned that this approval of Keytruda allows patients with stage 2b and 2c melanoma to consider their risks and provides them with “an option that (they) can consider taking to reduce (their) risk when (they) balance the pros and the cons of such an approach.”

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.