Adjuvant Pembrolizumab Wins European Approval for Stage IIB/IIC Melanoma Following Complete Resection

The European Commission has approved pembrolizumab for adjuvant treatment of adult and adolescent patients 12 years and older with stage IIB or IIC melanoma who have undergone a complete resection.

The European Commission (EC) has approved pembrolizumab (Keytruda) for adjuvant treatment of adult and adolescent patients 12 years and older with stage IIB or IIC melanoma who have undergone a complete resection.1

Furthermore, the EC expanded the indications for pembrolizumab to included adolescent patients aged 12 years and older with advanced unresectable or metastatic melanoma and stage III melanoma as an adjuvant treatment following complete resection.

“When melanoma recurs, patients often have a significantly worse long-term prognosis, especially if the cancer returns or spreads to distant sites,” Alexander Eggermont, MD, PhD, chief scientific officer of the Princess Máxima Center for Pediatric Oncology in the Netherlands, stated in a press release. “This approval further reinforces the important role of adjuvant therapy for patients 12 years and older with completely resected stage IIB and IIC melanoma who now have a treatment option that has demonstrated the potential to significantly reduce the risk of their cancer returning.”

The commission based its approval on findings from the phase 3 KEYNOTE-716 trial (NCT03553836) in which pembrolizumab significantly prolonged recurrence-free survival (RFS) vs placebo. At a median follow-up of 20.5 months, pembrolizumab reduced the risk of recurrence or death by 39% (HR, 0.61; 95% CI, 0.45-0.82; P= .00046). Additionally, at a median follow-up of 26.9 months, pembrolizumab lowered the risk of distant metastasis by 36% vs placebo (HR, 0.64; 95% CI, 0.47-0.88; P = .00292).

In December 2021, the FDA approved pembrolizumab for the adjuvant treatment of adult and pediatric patients with stage IIB or IIC melanoma following complete resection based on data from KEYNOTE-716.2

The trial enrolled 976 patients who were at least 12 years old with newly diagnosed, resected, high-risk, stage II melanoma with a negative sentinel lymph node biopsy. Patients were also required to have an ECOG performance status of 0 or 1.3

Patients were randomly assigned to 200 mg of intravenous (IV) pembrolizumab (n = 487) or IV placebo (n = 489) once every 3 weeks for 17 cycles. Stratification factors included T-category (3b, 4a, and 4b) and pediatric status.

The primary end point of the trial was RFS per investigator assessment. Secondary end points included distant metastasis–free survival, overall survival, and safety.

Additional data presented at the 2022 ASCO Annual Meeting showed that at a median follow-up of 37.2 months, patients in the pembrolizumab arm continued to see a benefit in RFS (HR, 0.64; 95% CI, 0.50-0.84).3The 24-month RFS rates in the pembrolizumab and placebo arms were 81.2% and 72.8%, respectively.

Investigators have evaluated single-agent pembrolizumab for safety in 7631 patients across multiple tumor types. The rate of any-grade immune-related adverse effects (IRAEs) in the adjuvant setting was 36.1% and the rate of grade 3-5 IRAEs was 8.9%. Investigators observed no new IRAEs with adjuvant pembrolizumab.

“Melanoma continues to be a public health burden in Europe, claiming more than 26,000 lives in 2020, with rates rising annually,” Scot Ebbinghaus, MD, vice president of Global Clinical Development at Merck Research Laboratories, said in a press release. “[Pembrolizumab] has become the first anti-PD-1 adjuvant treatment option approved in the EU for patients 12 years and older across stage IIB, IIC and III melanoma following complete resection, based on data that show the potential of [pembrolizumab] to help reduce the risk of recurrence, including as distant metastases, in these patients. This approval furthers our commitment to finding new effective options for even more patients with melanoma.”

References

  1. European Commission approves KEYTRUDA® (pembrolizumab) as adjuvant treatment for adult and adolescent patients (≥12 years of age) with stage IIB or IIC melanoma following complete resection. News release. Merck. June 24, 2022. Accessed June 24, 2022. https://bit.ly/3Nnppzg
  2. FDA approves Merck's KEYTRUDA (pembrolizumab) as adjuvant treatment for adult and pediatric (≥12 years of age) patients with stage IIB or IIC melanoma following complete resection. News release. Merck; December 3, 2021. Accessed June 24, 2022. https://bit.ly/3DrqYal
  3. Long GV, Luke JJ, Khattak M, et al. Distant metastasis-free survival with pembrolizumab versus placebo as adjuvant therapy in stage IIB or IIC melanoma: The phase 3 KEYNOTE-716 study. J Clin Oncol. 2022;40(suppl 17):LBA9500. doi:10.1200/JCO.2022.40.17_suppl.LBA9500