Ten-year data for Keytruda (pembrolizumab) demonstrates sustained overall survival benefit versus ipilimumab in advanced melanoma

Based on 10 years of follow-up, the data showed sustained improved survival outcomes for patients receiving Keytruda as a single agent compared to ipilimumab in patients with advanced melanoma. These late-breaking data will be presented for the first time today during a mini oral session at the European Society for Medical Oncology (ESMO) Congress 2024 (presentation #LBA44) and published in the Annals of Oncology.

For patients with advanced melanoma, these long-term follow-up data showed the 10-year OS rate for Keytruda was 34.0% versus 23.6% for ipilimumab. Keytrruda demonstrated a sustained OS benefit, reducing the risk of death by 29% (HR=0.71 [95% CI, 0.60-0.85]). At 10 years, Keytruda more than doubled the median OS compared to ipilimumab (32.7 months versus 15.9 months).

“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,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “Keytruda has reshaped the treatment of certain types of cancers, extending its benefits to a broader range of tumor types and patients, and we look forward to the prospect of more innovation for patients over the next 10 years and beyond.”

“The prognosis for patients diagnosed with melanoma has been steadily improving, with a 30% reduction in mortality compared to a decade ago,” said Dr. Caroline Robert, head of dermatology at Gustave Roussy, Villejuif and Paris-Sud University Cancer Campus, Grand Paris. “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.”

To date, Keytruda has demonstrated sustained survival benefits of five years or more across multiple types of cancer, including certain types of melanoma (KEYNOTE-006, KEYNOTE-054), non-small cell lung cancer (KEYNOTE-189, KEYNOTE-407), head and neck cancer (KEYNOTE-048) and bladder cancer (KEYNOTE-045).

Based on the results from KEYNOTE-006 in December 2015, the U.S. Food and Drug Administration approved Keytruda for the treatment of patients with unresectable or metastatic melanoma.

Ten-year follow-up of KEYNOTE-006 patients (Presentation #LBA44)

KEYNOTE-006 (ClinicalTrials.gov, NCT01866319 ) was an open-label, randomized Phase 3 study comparing the efficacy and safety of Keytruda versus ipilimumab in participants with advanced melanoma. The primary endpoints for KEYNOTE-006 were progression-free survival (PFS) and OS. At the conclusion of the KEYNOTE-006 study, participants were eligible to transition to the KEYNOTE-587 (ClinicalTrials.gov, NCT03486873 ) extension study for long-term follow-up. The primary endpoint for KEYNOTE-587 is OS. Results being presented at ESMO include an analysis of the efficacy and safety outcomes for 211 former KEYNOTE-006 participants who transitioned to KEYNOTE-587 (Keytruda, n=159; ipilimumab, n=52) after 10 years of follow-up and an analysis of additional antitumor activity in patients who received a second course of Keytruda.

With a median follow-up of 123.7 months (range, 122.0-127.3) from the time of study entry in KEYNOTE-006 to data cutoff for KEYNOTE-587, Keytruda continued to demonstrate improved OS and PFS. Findings from this long-term follow-up showed that the median OS was 32.7 months (95% CI, 24.5-41.6) for Keytruda versus 15.9 months (95% CI, 13.3-22.0) for ipilimumab (HR=0.71 [95% CI, 0.60-0.85]). The 10-year OS rate was 34.0% for Keytruda versus 23.6% for ipilimumab. Median modified PFS was 9.4 months (95% CI, 6.7-11.6) for KEYTRUDA and 3.8 months (95% CI, 2.9-4.3) for ipilimumab (HR=0.64 [95% CI, 0.54-0.75]).

At the final primary analysis with a median follow-up of 32 months, KEYNOTE-006 showed that with Keytruda, 55.1% and 55.3% of patients were alive two years after starting treatment (every two weeks and three weeks, respectively), compared to 43.0% of patients receiving ipilimumab (HR=0.68 [95% CI, 0.53-0.87; p=0.0008] and HR=0.68 [95% CI, 0.53-0.86; p=0.0008], respectively).

Citation: "Pembrolizumab versus ipilimumab for advanced melanoma; 10 year follow up of the phase III KEYNOTE 006 study"  G.V. Long, M.S. Carlino, C. McNeil, A. Ribas, C. Gaudy-Marqueste, J. Schachter, M. Nyakas, D. Kee, T.M. Petrella, A. Blaustein, M. Lotem, A.M. Arance, A.I. Daud, O. Hamid, J. Larkin, L. Yao, R. Singh, R. Lal, C. Robert. Annals of Oncology In Press Journal Pre-Proof Published online: September 15, 2024.DOI: https://doi.org/10.1016/j.annonc.2024.08.2330.