Patients with stage 3 melanoma were 43% less likely to have a recurrence after a one-year course of the humanized antibody, pembrolizumab. Specifically, the 12-month recurrence-free survival rate for patients randomized to pembrolizumab was 75.4%, in contrast to the 61% for those randomized to placebo, according to a study presented at the American Association for Cancer Research Annual Meeting 2018 in Chicago and published online in The New England Journal of Medicine (Apr. 15, 2018).
“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,” said Dr. Alexander M. M. Eggermont, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France in a press release. “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.”
A total of 1,019 patients with stage 3 melanoma, who were at high risk of recurrence after surgery were randomized 1:1 to a flat dose of 200 milligrams of pembrolizumab or placebo. Participants were required to have either stage 3A melanoma (patients with stage N1a melanoma had to have at least one micro-metastasis measuring >1 mm in greatest diameter) or stage 3B or 3C disease, with no in-transit metastases as defined by the American Joint Committee on Cancer 2009 classification, 7th edition. As Dr. Eggermont explained, they received treatment every three weeks for a total of 18 doses, or until disease recurrence or unacceptable toxicity transpired.
After a median follow-up of 15 months, 135 of the 514 patients treated with pembrolizumab and 216 of the 505 patients treated with placebo had been diagnosed with recurrent disease or had died. Additionally, 14.7% of participants in the pembrolizumab group experienced adverse events related to the trial regimen, compared to 3.4% of patients in the placebo group. One treatment-related death due to myositis was also reported in the pembrolizumab group.
The study conducted by Dr. Alexander M.M. Eggermont (pictured above) and his colleagues received support from the European Organisation for Research and Treatment of Cancer (EORTC) and the pharmaceutical company, Merck. Photo courtesy of the American Association for Cancer Research.
The positive effects of the humanized antibody were similar when patients with PD-L1-positive and PD-L1-negative tumours were examined separately. Among the 852 patients with PD-L1-positive tumours, those on pembrolizumab were 46% less likely to have a recurrence or death event compared with those who were given placebo. Among the 116 patients with PD-L1-negative tumours, those randomized to pembrolizumab were 53% 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 Dr. 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.”