FDA Approves Keytruda for Melanoma Patients After Tumor Resection

The U.S. Food and Drug Administration has approved the use of Keytruda (pembrolizumab) as a treatment for melanoma patients with stage 3 disease — cancer cells have spread to the lymph nodes but not to distant organs — who have undergone complete resection of a tumor.

The approval is based on data from the KEYNOTE-054 Phase 3 trial (NCT02362594), where Keytruda treatment reduced the risk of disease recurrence or death by 43% compared to a placebo.

“In the fight against cancer, progress is made one step at a time, and today we’re pleased to take another important step — making Keytruda available as an adjuvant therapy for patients with stage III melanoma,” Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said in a press release. “At Merck, we are committed to transforming the treatment of cancer, as is exemplified by this important advance in the adjuvant treatment of melanoma.”

Keytruda, developed by Merck (known as MSD outside the United States and Canada) is an immune checkpoint inhibitor, meant to help the immune system do a better job of recognizing and fighting cancer. It binds to a protein called PD-1 on immune T cells, preventing interaction with its ligand, PD-L1, produced by cancer cells to avoid immune surveillance.

KEYNOTE-054, conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC), was designed to test Keytruda in a population of melanoma patients with stage 3 disease whose cancer had been removed during surgery, but who were at high risk for disease recurrence. Keytruda was given as an adjuvant treatment, meaning it was used to consolidate tumor clearance after surgery.

The trial included 1,019 patients, median age 54, who had undergone surgery for melanoma, including lymph node dissection, with or without radiation therapy within 13 weeks of entering the study.

Participants, 84% of whom were positive for the PD-L1 factor — a biomarker that often predicts responses to Keytruda — were randomly assigned Keytruda or a placebo, given every three weeks as an infusion for up to one year or until disease recurrence or unacceptable toxicity.

The trial’s main goal was to determine whether Keytruda could delay disease recurrence, both in the overall population and in patients with PD-L1-positive tumors. Secondary measures included the time to metastasis or death, overall survival, and incidence of adverse events.

Among patients receiving Keytruda, 75.4% remained alive and disease-free for one year or longer, compared to 61% of those on placebo, representing a 43% reduction in the risk of disease recurrence or death. For patients with PD-L1-positive tumors, Keytruda reduced this risk by 46%.

Keytruda also reduced the risk of disease spreading by 47%, with 16.7% of patients developing a metastasis as the first site of recurrence within 18 months, compared to 29.7% for placebo.

Overall, more patients on Keytruda experienced serious adverse events — 14.7% versus 3.4% — with one patient dying because of chronic, progressive inflammation in the muscles caused by Keytruda. Its safety profile, however, was consistent with that already defined for it.

“As physicians, we are always looking to find ways to prevent cancer from returning in our patients,” said Alain Algazi, MD, associate clinical professor of medicine, Department of Medicine, Hematology/Oncology, University of California-San Francisco Medical Center. “Keytruda has demonstrated significant improvement in recurrence-free survival among stage III melanoma patients when compared to a placebo, and we now have a new option to help patients who have a high risk of recurrence.”