Merck's Keytruda (pembrolizumab) continues to demonstrate a significant overall survival (OS) benefit compared to ipilimumab in patients with advanced melanoma, according to 10-year follow-up data from the Phase 3 KEYNOTE-006 trial. These findings, presented at the European Society for Medical Oncology (ESMO) Congress 2024, underscore the long-term efficacy and impact of Keytruda in reshaping the treatment landscape for advanced melanoma.
The KEYNOTE-006 trial was an open-label, randomized study comparing the efficacy and safety of Keytruda versus ipilimumab in patients with advanced melanoma. The primary endpoints were progression-free survival (PFS) and OS. Patients completing KEYNOTE-006 were eligible to enroll in the KEYNOTE-587 extension study for long-term follow-up.
Sustained Overall Survival
After a median follow-up of 123.7 months, the 10-year OS rate for Keytruda was 34.0% compared to 23.6% for ipilimumab. Keytruda reduced the risk of death by 29% (HR=0.71 [95% CI, 0.60-0.85]). The median OS was 32.7 months for Keytruda versus 15.9 months for ipilimumab.
Dr. Caroline Robert, head of dermatology at Gustave Roussy, noted, "These latest data from KEYNOTE-006 illustrate the progress we’ve made in patient care. It is remarkable to see that more than one-third of patients treated with Keytruda are still alive today, 10 years after treatment."
Progression-Free Survival
Keytruda also demonstrated improved progression-free survival (PFS). The median modified PFS was 9.4 months for Keytruda versus 3.8 months for ipilimumab (HR=0.64 [95% CI, 0.54-0.75]).
Safety Profile
In KEYNOTE-006, Keytruda was discontinued due to adverse reactions in 9% of patients with advanced melanoma. Adverse reactions leading to permanent discontinuation included colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Common adverse reactions (≥20%) were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).
Impact on Melanoma Treatment
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. In the U.S., it is estimated there will be more than 100,640 new cases of melanoma diagnosed and more than 8,290 deaths resulting from the disease in 2024. The five-year survival rate for distant metastatic (Stage IV) melanoma is 22.5% as of 2018.
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, stated, "Ten years ago, KEYTRUDA became the first anti-PD-1/L1 therapy approved in the United States, setting the stage for transformative breakthroughs in the treatment of advanced melanoma and other types of cancer."
Keytruda's Broad Impact
Keytruda has demonstrated sustained survival benefits of five years or more across multiple cancer types, including certain types of melanoma, non-small cell lung cancer, head and neck cancer, and bladder cancer.
