Like the EORTC 18071 trial, KEYNOTE-054 (EORTC 1325) enrolled adults with completely resected stage III cutaneous melanoma. Patients with stage IIIa disease were high-risk, with sentinel node tumors exceeding 1-mm diameter per Rotterdam criteria. Stage IIIB or IIIC patients had no in-transit metastases. In all, 1,015 patients received up to 18 doses of pembrolizumab (200 mg infused every 3 weeks) or placebo for approximately 1 year. Relapsers could either repeat pembrolizumab or cross over to the pembrolizumab arm.
Treatment-related adverse events occurred in 78% of pembrolizumab patients and 66% of placebo recipients. As in prior studies, the most frequent adverse effects of pembrolizumab included fatigue or asthenia (37%), skin reactions (28%), diarrhea (19%), arthralgia (12%), nausea (11%), and dyspnea (6%). Rates of immune-related adverse events of any grade were 37% versus 9%. The most common immune-related adverse event was endocrinopathy (23%), specifically hypothyroidism (14%) and hyperthyroidism (10%). Grade 3 or higher toxicities affected 15% of pembrolizumab recipients and most often consisted of colitis (2%), endocrine disorders (1.8%), or hepatobiliary disorders (1.4%). Myositis caused the only pembrolizumab-related death.
Patients and clinicians await KEYNOTE-054 readouts on distant metastasis-free survival and overall survival. In past trials of adjuvant interferon alfa or ipilimumab for high-risk melanoma, RFS and overall survival closely correlated, Dr. Eggermont noted. KEYNOTE-54 can be expected to produce similar findings unless post-relapse therapy – including crossover to the pembrolizumab arm – narrows the survival advantage of adjuvant treatment, he added.
Merck makes pembrolizumab and funded the trial. Dr. Eggermont disclosed ties to Actelion, Agenus, Bayer, BMS, Incyte, ISA Pharmaceuticals, HalioDX, Merck-Serono, MSD, Nektar, Novartis, Pfizer, and Sanofi outside the submitted work.
SOURCE: Eggermont AMM et al. AACR Annual Meeting .