Jedd D Wolchok1, Vanna Chiarion-Sileni2, Rene Gonzalez3, Jean-Jacques Grob4, Piotr Rutkowski5, Christopher D Lao6, C Lance Cowey7, Dirk Schadendorf8, John Wagstaff9, Reinhard Dummer10, Pier Francesco Ferrucci11, Michael Smylie12, Marcus O Butler13, Andrew Hill14, Ivan Márquez-Rodas15, John B A G Haanen16, Massimo Guidoboni17, Michele Maio18, Patrick Schöffski19, Matteo S Carlino20, Céleste Lebbé21, Grant McArthur22, Paolo A Ascierto23, Gregory A Daniels24, Georgina V Long25, Tuba Bas26, Corey Ritchings26, James Larkin27, F Stephen Hodi28. 1. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY. 2. Venteo Institute of Oncology IOV-IRCCS, Padua, Italy. 3. University of Colorado Cancer Center, Aurora, CO. 4. Aix-Marseille University, APHM Timone France, Marseille, France. 5. Maria Sklodowska-Curie National Institute of Oncology Center, Warsaw, Poland. 6. University of Michigan, Ann Arbor, MI. 7. Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX. 8. University of Essen, Essen, and German Cancer Consortium, Heidelberg, Germany. 9. The College of Medicine, Swansea University, Swansea, United Kingdom. 10. Universitäts Spital Zürich, Zürich, Switzerland. 11. European Institute of Oncology IRCCS, Milan, Italy. 12. Cross Cancer Institute, Edmonton, Alberta, Canada. 13. Princess Margaret Cancer Centre, Toronto, Ontario, Canada. 14. Tasman Oncology Research, Southport, Queensland, Australia. 15. Hospital General Universitario Gregorio Marañon, Madrid, Spain. 16. Netherlands Cancer Institute, Amsterdam, the Netherlands. 17. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy. 18. Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy. 19. University Hospitals Leuven, Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium. 20. Westmead and Blacktown Hospitals, University of Sydney, Melanoma Institute Australia, Sydney, Australia. 21. Université de Paris, Department of Dermatology and CIC, AP-HP Hôpital Saint Louis, INSERM U976, Paris, France. 22. Peter MacCallum Cancer Centre, East Melbourne, Australia. 23. Melanoma Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy. 24. UC San Diego Health - La Jolla, La Jolla, CA. 25. Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, Australia. 26. Bristol Myers Squibb, Princeton, NJ. 27. The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom. 28. Dana-Farber Cancer Institute, Boston, MA.
Abstract
PURPOSE: In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. PATIENTS AND METHODS: Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated. RESULTS: Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF-wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed. CONCLUSION: These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.
PURPOSE: In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. PATIENTS AND METHODS: Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated. RESULTS: Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF-wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed. CONCLUSION: These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.
Authors: Vincent T Ma; Alahendra A Chamila Perera; Yilun Sun; Merna Sitto; Jessica J Waninger; Govind Warrier; Michael D Green; Leslie A Fecher; Christopher D Lao Journal: Front Immunol Date: 2022-07-06 Impact factor: 8.786
Authors: Paolo A Ascierto; Allison Betof Warner; Christian Blank; Corrado Caracò; Sandra Demaria; Jeffrey E Gershenwald; Nikhil I Khushalani; Georgina V Long; Jason J Luke; Janice M Mehnert; Caroline Robert; Piotr Rutkowski; Hussein A Tawbi; Iman Osman; Igor Puzanov Journal: J Transl Med Date: 2022-05-10 Impact factor: 8.440
Authors: Emily R Trzeciak; Niklas Zimmer; Isabelle Gehringer; Lara Stein; Barbara Graefen; Jonathan Schupp; Achim Stephan; Stephan Rietz; Michael Prantner; Andrea Tuettenberg Journal: Cells Date: 2022-03-08 Impact factor: 6.600