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

doi:10.1016/j.annonc.2024.08.2330

Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study

Ann Oncol. 2024 Sep 15:S0923-7534(24)03910-3. doi: 10.1016/j.annonc.2024.08.2330. Online ahead of print.

Authors

G V Long¹, M S Carlino², C McNeil³, A Ribas⁴, C Gaudy-Marqueste⁵, J Schachter⁶, M Nyakas⁷, D Kee⁸, T M Petrella⁹, A Blaustein¹⁰, M Lotem¹¹, A M Arance¹², A I Daud¹³, O Hamid¹⁴, J Larkin¹⁵, L Yao¹⁶, R Singh¹⁶, R Lal¹⁶, C Robert¹⁷

Affiliations

¹ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine & Health, The University of Sydney, Sydney, Australia; Charles Perkins Centre, The University of Sydney, Sydney, Australia; Royal North Shore and Mater Hospitals, Sydney, Australia. Electronic address: georgina.long@sydney.edu.au.
² Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine & Health, The University of Sydney, Sydney, Australia; Westmead and Blacktown Hospitals, Sydney, Australia.
³ Chris O'Brien Lifehouse, Camperdown, Australia.
⁴ Jonsson Comprehensive Cancer Center at The University of California Los Angeles (UCLA), Los Angeles, USA.
⁵ Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, CRCM La Timone Hospital, Dermatology and Skin Cancer Department, Marseille, France.
⁶ Sheba Medical Center-Tel HaShomer, Ramat Gan, Israel.
⁷ Oslo University Hospital, Oslo, Norway.
⁸ Austin Health, Heidelberg, Australia.
⁹ Sunnybrook Health Sciences Centre, Toronto, Canada.
¹⁰ Mount Sinai Medical Center Comprehensive Cancer Center, Miami Beach, USA.
¹¹ Sharett Institute of Oncology, Hadassah University Hospital Ein Kerem, Jerusalem, Israel.
¹² Hospital Clinic Barcelona and IDIBAPS, Barcelona, Spain.
¹³ Melanoma & Skin Cancer Center, University of California San Francisco, San Francisco.
¹⁴ The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, USA.
¹⁵ The Royal Marsden NHS Foundation Trust, London, UK.
¹⁶ Merck & Co., Inc., Rahway, USA.
¹⁷ Gustave Roussy and Paris-Saclay University, Villejuif, France. Electronic address: caroline.robert@gustaveroussy.fr.

PMID: 39306585
DOI: 10.1016/j.annonc.2024.08.2330

Abstract

Background: Pembrolizumab significantly improved overall survival (OS) versus ipilimumab for unresectable advanced melanoma in KEYNOTE-006 (NCT01866319); 10-year follow-up data are presented.

Patients and methods: Patients with unresectable stage III or IV melanoma were randomly assigned (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 weeks or every 3 weeks for ≤2 years (pooled), or ipilimumab 3 mg/kg i.v. every 3 weeks for four cycles. After KEYNOTE-006, patients could transition to KEYNOTE-587 (NCT03486873) for long-term follow-up. Eligible patients could receive second-course pembrolizumab. The primary endpoint was OS; modified progression-free survival (PFS; censored at date last known alive), modified PFS on second-course pembrolizumab, and melanoma-specific survival were exploratory.

Results: Of 834 patients randomly assigned in KEYNOTE-006 (pembrolizumab, n = 556; ipilimumab, n = 278), 333 (39.9%) were eligible for KEYNOTE-587; 211/333 patients (25.3%) transitioned to KEYNOTE-587 (pembrolizumab, n = 159; ipilimumab, n = 52) and 122 (14.6%) did not. For patients who transitioned to KEYNOTE-587 (n = 211), median time from randomization in KEYNOTE-006 to data cut-off for KEYNOTE-587 (1 May 2024) was 123.7 months (range, 122.0-127.3 months). Median OS was 32.7 months [95% confidence interval (CI) 24.5-41.6 months] for pembrolizumab and 15.9 months (95% CI 13.3-22.0 months) for ipilimumab [hazard ratio (HR), 0.71 (95% CI 0.60-0.85)]; 10-year OS was 34.0% and 23.6%, respectively. Among patients who completed ≥94 weeks of pembrolizumab, median OS from week 94 was not reached (NR; 95% CI NR-NR); 8-year OS rate was 80.8%. Median modified PFS was 9.4 months (95% CI 6.7-11.6 months) for pembrolizumab and 3.8 months (2.9-4.3 months) for ipilimumab [HR, 0.64 (95% CI 0.54-0.75)]. Among patients who received second-course pembrolizumab, median modified PFS from start of second course was 51.8 months (95% CI 11.0 months-NR); 6-year modified PFS was 49.2%. Median melanoma-specific survival was 51.9 months (95% CI 30.0-114.7 months) for pembrolizumab and 17.2 months (13.9-25.9 months) for ipilimumab [HR, 0.66 (95% CI 0.55-0.81)].

Conclusions: These results confirm that pembrolizumab provides long-term survival benefits in advanced melanoma, supporting it as a standard of care in this setting.

Keywords: immunotherapy; melanoma; pembrolizumab; phase III; programmed cell death protein 1.

Associated data

ClinicalTrials.gov/NCT01866319