On 15 February 2019, the FDA approved pembrolizumab (Keytruda®, Merck) for the adjuvant treatment of melanoma patients with lymph node involvement following complete resection.

EORTC1325/KEYNOTE-054

The double-blind, placebo-controlled EORTC1325/KEYNOTE‑054 (NCT02362594) trial randomised 1019 Stage IIIA (>1 mm lymph node metastasis), IIIB or IIIC melanoma patients 1:1 to receive pembrolizumab or placebo. All patients underwent complete resection of melanoma with negative margins, lymph node dissection, and radiotherapy (when indicated), within 13 weeks prior to initiating the study treatment. The study excluded patients with mucosal or ocular melanoma. The treatment lasted for up to one year or until recurrent disease or unacceptable toxicity. The primary efficacy endpoint was the investigator assessed recurrence‑free survival (RFS) per RECIST1.1, defined as the time between the date of randomisation and the first local, regional, or distant recurrence, or death due to any cause.

At the time of data cut-off, the median RFS with pembrolizumab was not yet reached and measured 20.4 months in the placebo arm. Patients receiving pembrolizumab had fewer recurrences and deaths, 26% (N=135) when compared with placebo; 43% (N=216) recurrences/deaths (HR=0.57; 95% CI, 0.46-0.70; P<0.001). The benefit in RFS for pembrolizumab was regardless of tumour PD-L1 expression.

Safety

The majority of patients (76%) received pembrolizumab for over 6 months. Discontinuation for adverse reactions occurred in 14% of pembrolizumab-treated patients. Common adverse reactions in ≥10% of pembrolizumab-treated patients included diarrhoea, pruritus, nausea, arthralgia, hypothyroidism, cough, rash, asthenia, influenza-like illness, weight loss, and hyperthyroidism.

Full prescribing information KEYTRUDA.