CHICAGO — A one-year course of 18 doses of pembrolizumab (Keytruda) significantly reduced the risk of recurrence for patients with stage 3 melanoma who were at high risk of recurrence after surgery, according to data from the KEYNOTE-054/EORTC 1325-MG phase III clinical trial, presented at the AACR Annual Meeting 2018, April 14–18.
This study is being published simultaneously in The New England Journal of Medicine.
“Patients with stage 3 melanoma have metastatic disease in one or more regional lymph nodes,” said Alexander M. M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France. “A patient’s risk of recurrence depends on the number of lymph nodes affected and the tumor load. Those classified as having a high risk of recurrence have one or more regional lymph nodes with melanoma metastasis. In the case of a single positive node, the diameter must be greater than 1 millimeter.
“We were pleased to see that adjuvant pembrolizumab, given as a flat dose of 200 milligrams every three weeks after surgery for up to a year, which is 18 doses, significantly reduced the risk of recurrence for patients with high-risk stage 3 melanoma that has been completely resected,” continued Eggermont. “We hope that these data will lead to regulators in the United States and Europe approving pembrolizumab as a new treatment option for these patients.”
For all the patients randomized to pembrolizumab, the 12-month recurrence-free survival rate was 75.4 percent, compared with 61.0 percent for all those randomized to placebo. Thus, overall, patients randomized to pembrolizumab were 43 percent less likely to have recurrence.
The FDA approved ipilumumab (Yervoy) and nivolumab (Opdivo) for use as an adjuvant treatment for patients with high-risk stage 3 melanoma that has been completely resected in October 2015 and December 2017, respectively.
Eggermont and colleagues enrolled 1,019 patients with stage 3 melanoma who were at high risk of recurrence after complete resection of their tumors in the KEYNOTE-054/EORTC 1325-MG phase III clinical trial. Patients were randomized 1:1 to a flat dose of 200 milligrams of pembrolizumab or placebo every three weeks for a total of 18 doses or until disease recurrence or unacceptable toxicity.
After a median follow-up of 1.25 years, 135 of the 514 patients randomized to pembrolizumab and 216 of the 505 patients randomized to placebo had been diagnosed with recurrent disease or had died.
The benefits of pembrolizumab were similar when patients with PD-L1-positive and PD-L1-negative tumors were analyzed separately. Among the 852 patients with PD-L1-positive tumors, those randomized to pembrolizumab were 46 percent less likely to have a recurrence or death event compared with those randomized to placebo. Among the 116 patients with PD-L1-negative tumors, those randomized to pembrolizumab were 53 percent less likely to have a recurrence or death event.
“An important aspect of this trial is that patients randomized to placebo who have recurrence are offered access to pembrolizumab,” said Eggermont. “This cross-over design is unique in the world of adjuvant trials in melanoma and will permit us to analyze if adjuvant therapy with pembrolizumab right after surgery is better or not than treating only those who relapse and start treatment at relapse.”
According to Eggermont, the main limitation of the study is that we need more time before we can determine whether these positive recurrence-free survival results will lead to improvement in overall survival for the patients.
This study was conducted by the European Organisation for Research and Treatment of Cancer (EORTC) and sponsored by Merck. Eggermont has received honoraria for scientific advisory board and data monitoring board functions from Actelion, Agenus, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, HalioDx, Incyte, ISA Pharmaceuticals, Merck, Merck Serono, Nektar, Novartis, Pfizer, and Sanofi.