Dirk Schadendorf1, Paolo A Ascierto2, John Haanen3, Enrique Espinosa4, Lev Demidov5, Claus Garbe6, Michele Guida7, Paul Lorigan8, Vanna Chiarion-Sileni9, Helen Gogas10, Michele Maio11, Maria Teresa Fierro12, Christoph Hoeller13, Patrick Terheyden14, Ralf Gutzmer15, Tormod K Guren16, Dimitrios Bafaloukos17, Piotr Rutkowski18, Ruth Plummer19, Ashita Waterston20, Martin Kaatz21, Mario Mandala22, Ivan Marquez-Rodas23, Eva Muñoz-Couselo24, Reinhard Dummer25, Elena Grigoryeva26, Tina C Young27, Paul Nathan28. 1. Department of Dermatology, University Hospital Essen, Essen, German Cancer Consortium, Heidelberg, Germany. Electronic address: Dirk.Schadendorf@uk-essen.de. 2. Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy. 3. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands. 4. Department of Medical Oncology, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain. 5. N.N. Blokhin Russian Cancer Research Centre, Ministry of Health, Moscow, Russia. 6. Division of Dermatologic Oncology, Department of Dermatology, Eberhard Karls University, Tübingen, Germany. 7. Department of Medical Oncology, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. 8. Institute of Cancer Sciences, University of Manchester, The Christie NHS Foundation Trust, Manchester, UK. 9. Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. 10. First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Laiko General Hospital, Athens, Greece. 11. Division of Medical Oncology and Immunotherapy, Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy. 12. Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy. 13. Department of Dermatology, Medical University of Vienna, Vienna, Austria. 14. Department of Dermatology, University of Lübeck, Lübeck, Germany. 15. Department of Dermatology, Hannover Medical School, Skin Cancer Centre Hannover, Hannover, Germany. 16. Department of Oncology, Oslo University Hospital, Oslo, Norway. 17. Department of Oncology, Metropolitan Hospital, Athens, Greece. 18. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute, Oncology Center, Warsaw, Poland. 19. Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne, United Kingdom. 20. Clinical Trials Unit, Beatson West of Scotland Cancer Centre, Glasgow, UK. 21. Department of Dermatology, SRH Wald Clinics, University Hospital, Gera, Germany. 22. Unit of Medical Oncology, Department of Oncology & Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy. 23. Medical Oncology Department, General University Hospital, Gregorio Marañón and CIBERONC, Madrid, Spain. 24. Medical Oncology, Vall D'Hebron University, Barcelona, Spain. 25. Department of Dermatology, Universitats Spital, Zürich, Switzerland. 26. Oncology Clinical Development, Bristol-Myers Squibb, Princeton, NJ, USA. 27. Global Biometric Sciences, Bristol-Myers Squibb, Princeton, NJ, USA. 28. Department of Medical Oncology, Mount Vernon Cancer Centre, London, United Kingdom.
Abstract
BACKGROUND: Limited data are available on nivolumab in challenging subgroups with advanced melanoma. We report outcomes of nivolumab after prior ipilimumab in patients who are typically excluded from clinical trials. PATIENTS AND METHODS: In this phase II, single-arm, open-label, multicentre study (CheckMate 172), patients with advanced melanoma who progressed on or after ipilimumab received nivolumab 3 mg/kg, every 2 weeks for up to 2 years. The primary objective was incidence of grade ≥3, treatment-related select adverse events (AEs). RESULTS: At a minimum follow-up of 18 months, grade ≥3 treatment-related select AEs with the most variation across subgroups were diarrhoea and colitis (1.1% [n = 11] and 0.3% [n = 3] for the total population [n = 1008]; 0.6% [n = 1] and 0.6% [n = 1] for patients with an asymptomatic central nervous system [CNS] metastasis [n = 165; 16.4%]; 4.5% [n = 3] and 3.0% [n = 2] for patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 2 [n = 66; 6.5%]; 2.4% [n = 2] and 0% for those who experienced a grade 3/4 immune-related AE [irAE] with prior ipilimumab [n = 84; 8.3%]; and 0% and 0% for autoimmune disease [n = 25; 2.5%], respectively). Median overall survival was 21.4 months in the total population and was 11.6, 2.4, 21.5, and 18.6 months in patients with a CNS metastasis, ECOG PS 2, a grade 3/4 irAE with prior ipilimumab, and autoimmune disease, respectively. CONCLUSIONS: In this large, phase II clinical trial of patients with advanced melanoma who progressed on or after ipilimumab, nivolumab demonstrated a safety profile consistent with that of prior clinical trials. ClinicalTrials.gov ID: NCT02156804.
BACKGROUND: Limited data are available on nivolumab in challenging subgroups with advanced melanoma. We report outcomes of nivolumab after prior ipilimumab in patients who are typically excluded from clinical trials. PATIENTS AND METHODS: In this phase II, single-arm, open-label, multicentre study (CheckMate 172), patients with advanced melanoma who progressed on or after ipilimumab received nivolumab 3 mg/kg, every 2 weeks for up to 2 years. The primary objective was incidence of grade ≥3, treatment-related select adverse events (AEs). RESULTS: At a minimum follow-up of 18 months, grade ≥3 treatment-related select AEs with the most variation across subgroups were diarrhoea and colitis (1.1% [n = 11] and 0.3% [n = 3] for the total population [n = 1008]; 0.6% [n = 1] and 0.6% [n = 1] for patients with an asymptomatic central nervous system [CNS] metastasis [n = 165; 16.4%]; 4.5% [n = 3] and 3.0% [n = 2] for patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 2 [n = 66; 6.5%]; 2.4% [n = 2] and 0% for those who experienced a grade 3/4 immune-related AE [irAE] with prior ipilimumab [n = 84; 8.3%]; and 0% and 0% for autoimmune disease [n = 25; 2.5%], respectively). Median overall survival was 21.4 months in the total population and was 11.6, 2.4, 21.5, and 18.6 months in patients with a CNS metastasis, ECOG PS 2, a grade 3/4 irAE with prior ipilimumab, and autoimmune disease, respectively. CONCLUSIONS: In this large, phase II clinical trial of patients with advanced melanoma who progressed on or after ipilimumab, nivolumab demonstrated a safety profile consistent with that of prior clinical trials. ClinicalTrials.gov ID: NCT02156804.
Authors: Vishal Navani; Moira C Graves; Hiren Mandaliya; Martin Hong; Andre van der Westhuizen; Jennifer Martin; Nikola A Bowden Journal: Cancer Treat Res Date: 2022