FDA Approves Adjuvant Pembrolizumab for Stage IIB or IIC Melanoma

Pembrolizumab for stage IIB or IIC melanoma has been granted approval by the FDA.

The FDA has granted approval to pembrolizumab (Keytruda) for the adjuvant treatment of both adult and pediatric patients aged 12 years and older with stage IIB or IIC melanoma following complete resection, according to a press release issued by Merck.

The approval is supported by results from the phase 3 KEYNOTE-716 clinical trial (NCT03553836), which primarily explored the investigator-assessed recurrence-free survival (RFS) of pembrolizumab compared with placebo in 976 patients with cutaneous stage IIB or IIC melanoma with negative sentinel lymph node biopsy. The secondary end points of the study were distant metastasis-free survival, overall survival, the incidence of adverse events (AEs), and the incidence of treatment discontinuation.

“The standard of care for patients with resected stage IIB and IIC melanoma has been observation, despite the fact that for these patients, the risk of recurrence is nearly the same as for patients with later-stage disease for whom treatment is recommended,” said Jason Luke, MD, director, Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, in a press release. “Today’s approval of pembrolizumab for the adjuvant treatment of patients 12 years and older with stage IIB and IIC melanoma following complete resection is an important advance that provides these patients with a new option that can help reduce the risk of their cancer returning.”

In the randomized, double-bind study, patients were assigned 1:1 to received either pembrolizumab 2 mg/kg intravenously every 3 weeks for up to 17 cycles or placebo on the same dosing schedule.2 

Results from the study were presented at the European Society of Medical Oncology Annual Meeting by Jason Luke, MD, FACP, an associate professor of medicine in the Division of Hematology/Oncology and the director of the Cancer Immunotherapeutics Center within the Immunology and Immunotherapy Program at UPMC Hillman Cancer Center. 

At a median follow-up of 14.4 months, treatment with pembrolizumab achieved a 35% reduction in the risk of disease recurrence of death compared with placebo (HR, 0.65; 95% CI 0.46-0.92; P =.00658). The median RFS has not yet be reached in either treatment arm. 

Results also showed that the recurrence developed in 11.1% of the pembrolizumab arm compared with 16.8% of the placebo arm. At 12 months, the RFS rate observed with pembrolizumab was 90.5% compared with 83.1% in the placebo arm.

Grade ≥3 AEs were seen in 25.9% of the patients treated with pembrolizumab compared with 17.1% of those given placebo. Further, there were grade ≥3 drug-related AEs reported in 16.1% versus 4.3%, respectively.

Treatment discontinuation occurred in 15.3% of the pembrolizumab-treated group versus only 2.5% of the patients who received placebo. The experimental treatment did not lead to any deaths during the study, but there were 4 deaths in the placebo arm.

Immune-mediated AEs were reported in 36.2% of the pembrolizumab arm versus 8.4% of the placebo arm. The most common immune-mediated AEs in the pembrolizumab arm versus the placebo arms were hypothyroidism (15.7% vs 3.5%) and hyperthyroidism (10.4% vs 0.6%). Many of the immune-mediated AEs observed were low grade.

Analyses in KEYNOTE-716 are ongoing but recruitment has been completed. Patients eligible for inclusion in the study were those with surgically resected and histologically/pathologically confirmed new diagnosis of stage IIB or stage IIC cutaneous melanoma who were naïve to treatment beyond surgical resection ≤ 12 weeks from the clinical trial site, showed no evidence of metastatic disease, and had an ECOG performance score of 0 or 1 or a Karnofsky performance score of ≥ 50 for participants ≤ 16 years old, or a Karnofsky Performance Scale (KPS) score ≥ 50 for participants >16 and < 18 years old. Patients must have also recovered well from any toxicity or complications related to surgery, and women could not be pregnant or breastfeeding and must have been using contraception.3

“Keytruda was the first anti-PD-1 therapy to be approved in metastatic melanoma in the United States seven years ago. Since then, we have built on this foundation in melanoma and have expanded the use of Keytruda into earlier stages of this disease,” said Scot Ebbinghaus, PhD vice president, clinical research, Merck Research Laboratories, in the press release. “With today’s approval, we can now offer healthcare providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC and stage III melanoma.”


1. FDA approves pembrolizumab for adjuvant treatment of Stage IIB or IIC melanoma. News release. FDA. December 3, 2021. Accessed December 3, 2021. https://bit.ly/3ImGFng
2. Luke JJ, Rutkowski P, Quierolo P, et al. LBA3_PR - 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. 2021;32(suppl 5): S1283-S1346. doi: 10.1016/annonc/annonc741
3. Safety and efficacy of pembrolizumab compared to placebo in resected high-risk stage ii melanoma (MK-3475-716/KEYNOTE-716). Clinicaltrials.gov. Accessed December 4, 2021.