AACR 2018: Adjuvant Pembrolizumab in High-Risk Stage III Melanoma


Key Points

  • Pembrolizumab significantly prolonged recurrence-free survival.
  • Significant benefit was observed in both PD-L1–positive and PD-L1–negative disease. 

As reported at the 2018 American Association for Cancer Research (AACR) Annual Meeting (Abstract CT001) and in The New England Journal of Medicine by Eggermont et al, the phase III EORTC 1325/KEYNOTE 054 trial has shown that adjuvant pembrolizumab (Keytruda) significantly prolonged recurrence-free survival vs placebo in patients with resected high-risk stage III melanoma.

Study Details

In the double-blind trial, 1,019 patients from 123 sites in 23 countries were randomized between August 2015 and November 2016 to receive pembrolizumab at 200 mg (n = 514) or placebo (n = 505) every 3 weeks for a total of 18 doses. Patients had to have either stage IIIA melanoma (those with stage N1a melanoma had to have ≥ 1 micrometastasis measuring > 1 mm in greatest diameter) or stage IIIB or IIIC disease with no in-transit metastases.

The primary endpoints were recurrence-free survival in the intention-to-treat population and in the subgroup of patients with programmed cell death ligand 1 (PD-L1)–positive disease (PD-L1 expression > 1%).

Recurrence-Free Survival

Median follow-up was 15 months. The recurrence-free survival rate at 1 year was 75.4% in the pembrolizumab group vs 61.0% in the placebo group (hazard ratio [HR] = 0.57, P < .001). Rates at 18 months were 71.4% vs 53.2%. Among the 853 patients with PD-L1–positive tumors, recurrence-free survival at 1 year was 77.1% vs 62.6% (HR = 0.54, P < .001). Pembrolizumab was also associated with significant benefit among 116 patients with PD-L1–negative tumors (1-year recurrence free survival = 72.2% vs 52.2%, HR = 0.47, P = .01). Hazard ratios favored pembrolizumab in all subgroups examined, including by disease stage, number of positive lymph nodes, and BRAF mutation status.

Adverse Events

Treatment-related grade ≥ 3 adverse events occurred in 14.7% of the pembrolizumab group vs 3.4% of the placebo group. Immune-related adverse events of any grade occurred in 37.3% vs 9.0%, including endocrine disorders in 23.4% vs 5.0%; the most common endocrine disorders in the pembrolizumab group were hypothyroidism (14.3%) and hyperthyroidism (10.2%).

Sarcoidosis occurred in 1.4% of pembrolizumab recipients. Grade 3 or 4 immune-related adverse events occurred in 7.1% of the pembrolizumab group and included colitis, hypophysitis or hypopituitarism, and type 1 diabetes mellitus. One treatment-related death, due to myositis, occurred in the pembrolizumab group.

The investigators concluded, “As adjuvant therapy for high-risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence-free survival than placebo, with no new toxic effects identified.”

The study was funded by Merck. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.