José María Piulats1,2,3, Enrique Espinosa3,4, Luis de la Cruz Merino5, Mar Varela6, Lorenzo Alonso Carrión7, Salvador Martín-Algarra8, Rafael López Castro9, Teresa Curiel10, Delvys Rodríguez-Abreu11, Miriam Redrado3, Montserrat Gomà6, Antonio José Rullán1, Alfonso Calvo González3, Alfonso Berrocal-Jaime12. 1. Medical Oncology Department, Catalan Institute of Cancer (ICO), IDIBELL-OncoBell, L'Hospitalet de Llobregat, Barcelona, Spain. 2. Clinical Research in Solid Tumors Group (CREST), Bellvitge Biomedical Research Institute IDIBELL-OncoBell, L'Hospitalet de Llobregat, Barcelona, Spain. 3. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. 4. Medical Oncology, Hospital Universitario La Paz, Madrid, Spain. 5. Medical Oncology, Hospital Universitario Virgen Macarena, Department of Medicine, Universidad de Sevilla, Sevilla, Spain. 6. Pathology Department, Hospital Universitari de Bellvitge (HUB), L'Hospitalet de Llobregat, Barcelona, Spain. 7. Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain. 8. Medical Oncology, Clínica Universidad de Navarra, Pamplona, Spain. 9. Medical Oncology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain. 10. Medical Oncology, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. 11. Medical Oncology, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain. 12. Medical Oncology, Complejo Hospitalario General Universitario de Valencia, Valencia, Spain.
Abstract
PURPOSE: This study aimed to assess the efficacy of the combination of nivolumab (nivo) plus ipilimumab (ipi) as a first-line therapy with respect to the 12-month overall survival (OS) in patients with metastatic uveal melanoma (MUM) who are not eligible for liver resection. METHODS: This was a single-arm, phase II trial led by the Spanish Multidisciplinary Melanoma Group (GEM) on nivo plus ipi for systemic treatment-naïve patients of age > 18 years, with histologically confirmed MUM, Eastern Cooperative Oncology Group-PS 0/1, and confirmed progressive metastatic disease (M1). Nivo (1 mg/kg once every 3 weeks) and ipi (3 mg/kg once every 3 weeks) were administered during four inductions, followed by nivo (3 mg/kg once every 2 weeks) until progressive disease, toxicity, or withdrawal. The primary end point was 12-month OS. OS, progression-free survival (PFS), and overall response rate were evaluated every 6 weeks using RECIST (v1.1). Safety was also evaluated. Logistic regression and Cox proportional hazard models comprising relevant clinical factors were used to evaluate the potential association with response to treatment and survival. Cytokines were quantified in serum samples for their putative role in immune modulation/angiogenesis and/or earlier evidence of involvement in immunotherapy. RESULTS: A total of 52 patients with a median age of 59 years (range, 26-84 years) were enrolled. Overall, 78.8%, 56%, and 32% of patients had liver M1, extra-liver M1, and elevated lactate dehydrogenase. Stable disease was the most common outcome (51.9%). The primary end point was 12-month OS, which was 51.9% (95% CI, 38.3 to 65.5). The median OS and PFS were 12.7 months and 3.0 months, respectively. PFS was influenced by higher LDH values. CONCLUSIONS: Nivo plus ipi in the first-line setting for MUM showed a modest improvement in OS over historical benchmarks of chemotherapy, with a manageable toxicity profile.
PURPOSE: This study aimed to assess the efficacy of the combination of nivolumab (nivo) plus ipilimumab (ipi) as a first-line therapy with respect to the 12-month overall survival (OS) in patients with metastatic uveal melanoma (MUM) who are not eligible for liver resection. METHODS: This was a single-arm, phase II trial led by the Spanish Multidisciplinary Melanoma Group (GEM) on nivo plus ipi for systemic treatment-naïve patients of age > 18 years, with histologically confirmed MUM, Eastern Cooperative Oncology Group-PS 0/1, and confirmed progressive metastatic disease (M1). Nivo (1 mg/kg once every 3 weeks) and ipi (3 mg/kg once every 3 weeks) were administered during four inductions, followed by nivo (3 mg/kg once every 2 weeks) until progressive disease, toxicity, or withdrawal. The primary end point was 12-month OS. OS, progression-free survival (PFS), and overall response rate were evaluated every 6 weeks using RECIST (v1.1). Safety was also evaluated. Logistic regression and Cox proportional hazard models comprising relevant clinical factors were used to evaluate the potential association with response to treatment and survival. Cytokines were quantified in serum samples for their putative role in immune modulation/angiogenesis and/or earlier evidence of involvement in immunotherapy. RESULTS: A total of 52 patients with a median age of 59 years (range, 26-84 years) were enrolled. Overall, 78.8%, 56%, and 32% of patients had liver M1, extra-liver M1, and elevated lactate dehydrogenase. Stable disease was the most common outcome (51.9%). The primary end point was 12-month OS, which was 51.9% (95% CI, 38.3 to 65.5). The median OS and PFS were 12.7 months and 3.0 months, respectively. PFS was influenced by higher LDH values. CONCLUSIONS:Nivo plus ipi in the first-line setting for MUM showed a modest improvement in OS over historical benchmarks of chemotherapy, with a manageable toxicity profile.
Authors: Richard D Carvajal; Marcus O Butler; Alexander N Shoushtari; Jessica C Hassel; Alexandra Ikeguchi; Leonel Hernandez-Aya; Paul Nathan; Omid Hamid; Josep M Piulats; Matthew Rioth; Douglas B Johnson; Jason J Luke; Enrique Espinosa; Serge Leyvraz; Laura Collins; Howard M Goodall; Koustubh Ranade; Chris Holland; Shaad E Abdullah; Joseph J Sacco; Takami Sato Journal: Nat Med Date: 2022-10-13 Impact factor: 87.241
Authors: Cornelia L A Dewald; Mia-Maria Warnke; Roland Brüning; Martin A Schneider; Peter Wohlmuth; Jan B Hinrichs; Anna Saborowski; Arndt Vogel; Frank K Wacker Journal: Cancers (Basel) Date: 2021-12-27 Impact factor: 6.639