FDA Approves Pembrolizumab for Adjuvant Treatment of Stage IIB or IIC Melanoma

Melanoma cells.

The FDA has approved pembrolizumab (Keytruda®, Merck), a programmed death cell death protein 1 (PD-1)–blocking antibody, for the adjuvant treatment of adult and pediatric patients 12 years and older with stage IIB or IIC melanoma following complete resection.

“Current standard of care for patients after resection of high-risk stage II melanoma is observation,” wrote Jason Luke, MD, Director of the Cancer Immunotherapeutics Center in the Division of Hematology/Oncology at the University of Pittsburgh Hillman Cancer Center, and colleagues in their 2021 European Society for Medical Oncology (ESMO) Congress abstract concerning results of KEYNOTE-716 (NCT03553836), a phase 3 clinical trial comparing pembrolizumab with placebo for melanoma. “In the phase 3 double-blind KEYNOTE-716 trial, we evaluated pembrolizumab versus placebo in patients with resected American Joint Committee on Cancer (AJCC)–8 stage IIB or IIC melanoma.”

This double-blind phase 3 clinical trial included 976 patients with stage IIB or IIC melanoma which had been completely resected, with negative sentinel lymph node biopsy. Patients were randomized 1:1 to receive pembrolizumab 200 mg (or 2 mg/kg for pediatric patients) or placebo intravenously once every three weeks for up to one year or until disease recurrence or unacceptable toxicity occurred. The primary end point was investigator-assessed recurrence-free survival.

At a median follow-up of 14.4 months, the trial demonstrated a statistically significant improvement in recurrence-free survival for patients receiving pembrolizumab compared with placebo, with a hazard ratio of 0.65 (P=0.00658). Median recurrence-free survival was not reached in either arm.

The most common adverse events reported in at least 20% of patients receiving pembrolizumab were fatigue, diarrhea, pruritis, arthralgia. Immune-mediated adverse events occurred in 36.2% of patients receiving pembrolizumab versus 8.4% of those receiving placebo; the most common immune-related adverse events were hypothyroidism (15.7% vs 3.5%) and hyperthyroidism (10.4% vs 0.6%). Most immune-mediated adverse events were grade 1 or 2 in severity.

“Adjuvant pembrolizumab for resected stage IIB and stage IIC melanoma decreased the risk of disease recurrence or death by 35% compared with placebo and was associated with significantly prolonged recurrence-free survival and a favorable benefit-risk profile,” concluded Dr. Luke and colleagues.

The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks for adult patients and 2 mg/kg every 3 weeks, up to a maximum dose of 200 mg, for pediatric patients, given as intravenous injection.

For More Information

Luke JJ, Rutkowski P, Queirolo P, et al (2021). Pembrolizumab versus placebo after complete resection of high-risk stage II melanoma: efficacy and safety results from the KEYNOTE-716 double-blind phase III trial. Ann Oncol (ESMO Congress Abstracts), 32(suppl_5). Abstract LBA3_PR. DOI:10.1016/annonc/annonc741

Clinicaltrials.gov (2021). Safety and efficacy of pembrolizumab compared to placebo in resected high-risk stage II melanoma (MK-3475-716/KEYNOTE-716). NLM identifier: NCT03553836.

Keytruda® (pembrolizumab) prescribing information (2021). Merck. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s112lbl.pdf

US Food & Drug Administration (2021). FDA approves pembrolizumab for adjuvant treatment of stage IIB or IIC melanoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-stage-iib-or-iic-melanoma

Image courtesy of Jensflorian. Licensed under CC BY-SA 3.0

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