EC approves KEYTRUDA® as adjuvant therapy

Syringe with liquid
KEYTRUDA's European Approval was based on significant recurrence-free survival benefit demonstrated in Pivotal Phase 3 trial.

MSD (Merck in the U.S. and Canada) has announced that the European Commission has approved its anti-PD-1 therapy, KEYTRUDA (pembrolizumab), for the adjuvant treatment of adults with stage III melanoma and lymph node involvement who have undergone complete resection.

This approval is based on data from the pivotal Phase 3 EORTC1325/KEYNOTE-054 trial, conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC).

This follows NICE’s guidance that recommends KEYTRUDA® (pembrolizumab) for use within the Cancer Drugs Fund as monotherapy for the adjuvant treatment of adults with stage III melanoma with lymph node involvement who have undergone complete resection. It is recommended only if the conditions in the managed access agreement for pembrolizumab are followed.

An updated recurrence-free survival (RFS) data analysis, conducted at the request of the European Medicines Agency, demonstrated that KEYTRUDA significantly prolonged RFS, reducing the risk of disease recurrence or death by 44% compared to placebo in the overall population of patients with resected, high-risk stage III melanoma (HR=0.56; 98% CI, 0.44-0.72; p<0.0001).

The approval allows marketing of KEYTRUDA in this new indication in all 28 EU member states plus Iceland, Lichtenstein and Norway, at the approved dose of 200 mg every three weeks until disease recurrence, unacceptable toxicity, or for a duration of up to one year. KEYTRUDA is also approved in Europe as a monotherapy for the treatment of advanced (unresectable or metastatic) melanoma in adults.

Melanoma is the most serious form of skin cancer and is characterised by the uncontrolled growth of pigment-producing cells. Worldwide, the incidence of melanoma has been increasing over the past four decades in many populations, and it is estimated that in 2018 there will be more than 287,000 new melanoma cases and over 60,000 people will die from the disease. In Europe, the five-year survival rate for advanced or metastatic melanoma (stage IV) is estimated to be about five to 22%.

Dr Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories, said: “This approval, which is the first for KEYTRUDA in the adjuvant setting in the European Union, builds upon the foundation established by KEYTRUDA in the advanced and metastatic melanoma settings.”

Dr Alexander Eggermont, study chair, Director General at the Gustave Roussy Cancer Institute, Professor of Oncology, University of Paris-Saclay, said: “Melanoma patients, particularly those with stage III disease, often have a high risk of recurrence, and the collaborative study from EORTC and Merck demonstrated a significant reduction in the risk of cancer returning after surgery.

“This approval in the adjuvant setting marks another important milestone in the treatment of melanoma.”

NICE’s approval is a milestone for a patient population where the current standard of care is routine surveillance (‘watch and wait’). The approval was based on data from the EORTC1325/KEYNOTE-054 trial, published in the New England Journal of Medicine in 2018.

Inclusion in the CDF shows that NICE considers pembrolizumab has potential to satisfy the criteria for routine use on the NHS for this group of melanoma patients but needs more investigation, through data collection in the NHS, before making a final decision on routine commissioning.

Imogen Cheese, Director, Melanoma Patient Conference CIC, said: “The introduction of this new stage in treatment brings about a shift in the mindset for treating melanoma long term. Historically, Stage III patients have been obliged to ‘watch and wait’ for advanced progression. A solution that has been a burden psychologically for many patients and their families.”

Gillian Nuttall, Melanoma UK: “The number of people with melanoma in the UK is continuing to rise, especially in younger people. The current ‘watch and wait’ approach after surgery can be a tense time for patients and their families, making this announcement even more important as we can begin to shift away from this. This is encouraging news for the patient population.”