Hello. I'm Dr Jeffrey Weber. I'm a medical oncologist at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health. Today I'll discuss a very interesting abstract on the KEYNOTE-054 study. The findings were recently presented at the American Association for Cancer Research annual meeting and published in the New England Journal of Medicine.
This adjuvant immunotherapy trial involved 1019 patients and was conducted by the European Organization for Research and Treatment of Cancer (EORTC). Patients with stage III A, B, and C resected melanoma were randomized 1:1 to receive the programmed death (PD-1) blocking antibody pembrolizumab or placebo. Overall, the two trial arms were well balanced, with a minimal imbalance in patients with macroscopic nodal resected disease. In each arm, 45% of patients had BRAF wild-type melanoma, and a little over 50% were BRAF mutated, which is quite important.
This very impressive, well-conducted, well-powered trial was clearly positive for the pembrolizumab arm. The data clearly show an advantage for pembrolizumab, with a hazard ratio of 0.57 for overall relapse-free survival, with 15 months of follow-up in all patients. The 12-month relapse-free survival was 75% in the pembrolizumab arm and 61% in the placebo arm. At 18 months, those numbers were 71% and 53%, which reflects an 18% absolute difference in relapse-free survival—again, a very impressive number.
The groups were broken down by a number of parameters, including programmed cell death ligand 1 (PD-L1) and BRAF status, as well as by stage, and all subgroups benefited from pembrolizumab adjuvant therapy. Patients with PD-L1-positive tumors had a hazard ratio for recurrence of 0.54. Patients with PD-L1-negative tumors, whom you might think might not benefit as much, had a hazard ratio for recurrence of 0.47. Patients with PD-L1-positive cancer did better, with a 12-month relapse-free survival of 77% compared with 72% for PD-L1- negative patients. Nonetheless, there was clear benefit for both subgroups.
Stage IIIA patients, who generally have a very good outlook, had a hazard ratio of 0.32, which is outstanding. When you break it down by BRAF V600-mutated versus BRAF wild-type, the hazard ratios were still excellent: 0.57 versus 0.64. Again, in the forest plot, virtually all subgroups of patients had clear benefit from pembrolizumab, with superb hazard ratios.
Roughly 10% of patients in the pembrolizumab arm had local regional recurrence compared with 15% in the placebo arm. If distant metastasis [was included] as relapse, either alone or with local regional disease, the recurrence rates were 25% in the placebo arm and 15% in the pembrolizumab arm. Because distant metastasis-free survival is a surrogate for overall survival, I have high hopes that with adequate follow-up we will see a significant benefit in survival. In the data listed, very, very few patients have died thus far, [but this is] with only about 15 months of follow-up in all patients.
In terms of toxicity, as one might expect, pembrolizumab was very well tolerated. About 13% of patients stopped treatment because of an adverse event. The rate of grade III/IV adverse events, immune-related or not, was 14.7%. These data are quite similar to those seen with the use of the FDA-approved nivolumab in a somewhat similar, but worse-risk, patient population.
Overall, the data very definitively both confirm and extend the benefit of adjuvant PD-1 blockade in patients with high-risk, stage III A, B, and C resected melanoma.
Medscape Oncology © 2018 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Jeffrey S. Weber. Adjuvant Immunotherapy Improves Recurrence-Free Survival in Melanoma in KEYNOTE-054 - Medscape - Jul 17, 2018.