Decade-Long Data Show KEYTRUDA® Outperforms Ipilimumab in Advanced Melanoma Survival

Merck, operating as MSD internationally, has unveiled significant long-term survival data from the KEYNOTE-006 trial, focusing on their anti-PD-1 therapy, KEYTRUDA (pembrolizumab), for advanced melanoma patients. The study, which monitored patients for a decade, indicates that those treated with KEYTRUDA experienced markedly better survival outcomes compared to those treated with ipilimumab.

Presented at the European Society for Medical Oncology (ESMO) Congress 2024, and published in the Annals of Oncology, the data highlights that KEYTRUDA achieved a 10-year overall survival (OS) rate of 34.0%, surpassing ipilimumab's 23.6%. Furthermore, KEYTRUDA reduced the risk of death by 29%, with a hazard ratio (HR) of 0.71. The median OS for KEYTRUDA was 32.7 months, significantly higher than ipilimumab's 15.9 months.

Dr. Marjorie Green, a senior executive at Merck Research Laboratories, emphasized that KEYTRUDA set a precedent in cancer immunotherapy upon its approval in the U.S. a decade ago, leading to significant advancements in treating not only melanoma but various cancers. Dr. Caroline Robert, a prominent dermatologist at Gustave Roussy Cancer Campus, highlighted the improved prognosis for melanoma patients, noting a 30% reduction in mortality over the past decade. She praised the KEYNOTE-006 results, which showed over a third of patients treated with KEYTRUDA were still alive after ten years.

KEYTRUDA's efficacy extends beyond melanoma, demonstrating sustained survival benefits across multiple cancer types, including non-small cell lung cancer, head and neck cancer, and bladder cancer. Based on KEYNOTE-006 results, the U.S. FDA approved KEYTRUDA for unresectable or metastatic melanoma in December 2015.

The KEYNOTE-006 trial (ClinicalTrials.gov, NCT01866319) was a pivotal Phase 3 study comparing KEYTRUDA and ipilimumab in advanced melanoma patients, with primary endpoints being progression-free survival (PFS) and OS. Participants from KEYNOTE-006 were eligible for long-term follow-up in the KEYNOTE-587 extension study (ClinicalTrials.gov, NCT03486873). With a median follow-up of over 123 months, KEYTRUDA continued to show enhanced OS and PFS. Median OS was 32.7 months for KEYTRUDA versus 15.9 months for ipilimumab, and the 10-year OS rates were 34.0% and 23.6%, respectively. Median modified PFS was also better with KEYTRUDA at 9.4 months compared to 3.8 months for ipilimumab.

Melanoma remains the most serious form of skin cancer, characterized by the uncontrolled growth of pigment-producing cells. The incidence of melanoma has been increasing globally, with an estimated 331,650 new cases in 2022. In the U.S., melanoma is a significant cause of skin cancer deaths, with over 100,640 new cases and 8,290 deaths expected in 2024. The five-year survival rate for distant metastatic melanoma was estimated at 22.5% as of 2018.

KEYTRUDA works by enhancing the immune system's ability to detect and combat tumor cells, blocking the interaction between the PD-1 receptor and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes. Merck's clinical research program for KEYTRUDA is one of the largest in the industry, with over 1,600 trials covering various cancers and treatment settings. The program aims to understand the factors that predict a patient's response to KEYTRUDA, including different biomarkers.