FDA Approves Pembrolizumab for Adjuvant Treatment of Melanoma

February 19, 2019
FDA Approves Pembrolizumab for Adjuvant Treatment of Melanoma

On February 15, 2019, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. 

Approval was based on EORTC1325/KEYNOTE‑054 (NCT02362594), a randomized, double-blind, placebo-controlled, trial in 1,019 patients with completely resected, stage IIIA (>1 mm lymph node metastasis), IIIB or IIIC melanoma (https://cancerstaging.org/CSE/Physician/Pages/Articles.aspx). Patients with mucosal or ocular melanoma were not eligible. Patients were randomly allocated (1:1) to receive pembrolizumab 200 mg every three weeks or placebo for up to one year until disease recurrence or unacceptable toxicity. Enrollment required complete resection of melanoma with negative margins, lymph node dissection, and completion of radiotherapy, if indicated, within 13 weeks prior to starting treatment.

The primary efficacy outcome measure was recurrence‑free survival (RFS), as assessed by investigators per RECIST version 1.1. RFS was defined as the time between the date of randomization and first recurrence (local, regional, or distant metastasis) or death from any cause, whichever occurred first. Patients receiving pembrolizumab experienced fewer recurrences/deaths, 26% (n=135), compared with 43% (n=216) on the placebo arm (hazard ratio 0.57; 95% CI: 0.46, 0.70; p<0.001). The RFS benefit for pembrolizumab compared with placebo was observed regardless of tumor PD-L1 expression. Median RFS was 20.4 months in the placebo arm and not reached for those receiving pembrolizumab.

Seventy-six percent of patients received pembrolizumab for six months or longer. Pembrolizumab was discontinued for adverse reactions in 14% of patients. The most common adverse reactions (https://voice.ons.org/conferences/managing-immunotherapy-related-adverse-events) (reported in at least 10% of pembrolizumab-treated patients) were diarrhea, pruritus, nausea, arthralgia, hypothyroidism, cough, rash, asthenia, influenza-like illness, weight loss, and hyperthyroidism.

The recommended pembrolizumab dose and schedule for the adjuvant treatment of melanoma is 200 mg administered as an IV infusion over 30 minutes every three weeks until disease recurrence or unacceptable toxicity, for a maximum of one year.

View full prescribing information for pembrolizumab (https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125514s040lbl.pdf).

FDA granted this application standard review and Orphan Designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (http://www.fda.gov/medwatch/report.htm) or by calling 1-800-FDA-1088.

In collaboration with the FDA and as a service to our members, ONS provides updates on recent FDA approvals and other important FDA actions (e.g., updated safety information, new prescribing information) pertaining to therapies for patients with cancer. This allows the agency to inform oncologists and professionals in oncology-related fields in a timely manner. Included in the FDA updates is a link to the product label or to other sites for additional relevant clinical information. In supplying this information, ONS does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.


Copyright © 2019 by the Oncology Nursing Society. User has permission to print one copy for personal or unit-based educational use. Contact pubpermissions@ons.org for quantity reprints or permission to adapt, excerpt, post online, or reuse ONS Voice content for any other purpose.