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FDA Accepts Application for Adjuvant Pembrolizumab for Stage III Melanoma

Jason M. Broderick @jasoncology
Published: Monday, Jun 25, 2018

The FDA has accepted a supplemental biologics license application (sBLA) for the use of pembrolizumab (Keytruda) as an adjuvant treatment for patients with resected, high-risk stage III melanoma, according to Merck (MSD), the manufacturer of the PD-1 inhibitor.

= .0009). The 18-month RFS rates were 69.2% versus 52.4%, respectively.

Among BRAF wild-type patients, the 1-year RFS rate was 73.0% with pembrolizumab versus 59.7% with placebo (HR, 0.64; 99% CI, 0.42-0.96; = .0039). The 18-month RFS rates were 66.7% versus 48.8%, respectively. 

Grade 3 to 5 treatment-related adverse events (AEs) occurred in 14.7% of the pembrolizumab arm versus 3.4% of the placebo group. In the pembrolizumab arm, there was 1 treatment-related death due to myositis.

All-grade immune-related AEs were reported in 37.3% of the pembrolizumab group and 9.0% of the placebo group. The incidence of endocrine disorders was higher with pembrolizumab (23.4% vs 5.0), with the most common endocrine disorders being hypothyroidism (14.3% vs 2.8%) and hyperthyroidism (10.2% vs 1.2%). The incidence of these 2 AEs was mostly grade 1 or 2, except for 1 case of grade 3 hyperthyroidism. Sarcoidosis also occurred at a low rate (1.4% vs 0%), with all cases being grade 1 or 2. 

Grade 3/4 immune-related AEs occurred in 7.1% versus 0.6% of patients in the pembrolizumab versus placebo arms respectively. Events occurring at rates >1% included colitis (2.0% vs 0.2%), pneumonitis (0.8% vs 0%), and hepatitis (1.4% vs 0.2%).

“The EORTC 1325 trial will continue to its secondary end points, distant metastasis-free survival and overall survival. We recently found that the effects of treatment on recurrence-free survival correlate very well with the effects on overall survival in trials of adjuvant therapy with interferon alfa and with ipilimumab in high-risk melanoma,” Eggermont et al wrote in the NEJM publication of their findings.

“Therefore, one may reasonably expect that the benefit of pembrolizumab for relapse-free survival that we have found in our trial will translate into an overall survival benefit, unless effective post-relapse treatments compensate for the initial disadvantage; this is a question that may be answered by the crossover design of the trial,” continued Eggermont et al.


  1. Egermont AMM, Blank CU, Mandala M, et al. Pembrolizumab vs. placebo after complete resection of high-risk stage iii melanoma: efficacy and safety results from the EORTC 1325-MG/KEYNOTE-054 double-blinded phase 3 trial. Presented at 2018 AACR Annual Meeting; April 14-18, 2018; Chicago, Illinois. Abstract CT001.
  2. Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma [published online April 15, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1802357.


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