On December 3, 2021, pembrolizumab was approved for adjuvant treatment of adult and pediatric (≥ 12 years of age) patients with stage IIB or IIC melanoma following complete resection.1
Supporting Efficacy Data
Approval was based on findings in the phase III, double-blind KEYNOTE-716 trial (ClinicalTrials.gov identifier NCT03553846), in which 976 patients were randomly assigned to pembrolizumab at 200 mg or a pediatric (≥ 12 years) dose of 2 mg/kg (maximum = 200 mg) every 3 weeks (n = 487) or placebo (n = 489) for up to 1 year or until disease recurrence or unacceptable toxicity.
At first interim analysis, investigator-assessed recurrence-free survival events had occurred in 54 patients (11%) in the pembrolizumab group vs 82 patients (17%) in the placebo group (hazard ratio = 0.65, 95% confidence interval = 0.46–0.92, P = .0132). Median recurrence-free survival was not reached (95% CI = 22.6 months to not reached) vs not reached (95% CI = not reached to not reached).
How It Is Used
The recommended dose of pembrolizumab in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks in adults and 2 mg/kg every 3 weeks (to maximum of 200 mg) in pediatric patients until disease recurrence, unacceptable toxicity, or up to 12 months.
No dose reductions of pembrolizumab are recommended. In general, pembrolizumab should be withheld for grade 3 immune-mediated adverse reactions and permanently discontinued for grade 4 immune-mediated adverse reactions, recurrent grade 3 immune-mediated reactions requiring systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to ≤ 10 mg prednisone or equivalent per day within 12 weeks of initiating steroids. Prescribing information provides instructions on dosage modifications for immune-mediated adverse reactions and infusion-related reactions.
The most common adverse events of any grade (≥ 20% of patients) in trials of single-agent pembrolizumab have been fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism. The most common adverse events of any grade with pembrolizumab in KEYNOTE-716 (≥ 20%) were fatigue, diarrhea, pruritus, and arthralgia.
Prescribing information does not provide a detailed account of adverse events in KEYNOTE-716. Adverse events were similar to those occurring with single-agent pembrolizumab in 1,011 patients with stage III melanoma in KEYNOTE-054 and in 2,799 patients with melanoma or non–small cell lung cancer.
Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic reactions, and solid organ transplant rejection; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving pembrolizumab.
1. Keytruda (pembrolizumab) injection for intravenous use prescribing information, Merck & Co, December 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s112lbl.pdf. Accessed December 10, 2021.