Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial

Autor: Mazhar Ajaz, Laurent Mortier, Inge Marie Svane, Ivan Marquez-Rodas, Thomas Eigentler, Jennifer Lord-Bessen, Paolo A. Ascierto, Elena Grigoryeva, Dirk Schadendorf, Caroline Robert, Linda Rollin, Jacopo Pigozzo, Nicolas Meyer, Michael Smylie, Rene Gonzalez, Alexander M. Menzies, Piotr Rutkowski, Céleste Lebbé, Abdel Saci
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Skin Neoplasms
Time Factors
Medizin
Gastroenterology
law.invention
0302 clinical medicine
Antineoplastic Agents
Immunological
Randomized controlled trial
law
Skin Neoplasms/drug therapy
Antineoplastic Combined Chemotherapy Protocols
Clinical endpoint
Melanoma/drug therapy
Ipilimumab/administration & dosage
Melanoma
Aged
80 and over
Antineoplastic Combined Chemotherapy Protocols/administration & dosage
Middle Aged
Progression-Free Survival
3. Good health
Nivolumab/administration & dosage
Nivolumab
Oncology
030220 oncology & carcinogenesis
Disease Progression
Female
Rapid Communication
medicine.drug
Adult
medicine.medical_specialty
Ipilimumab
Drug Administration Schedule
03 medical and health sciences
Young Adult
Antineoplastic Agents
Immunological/administration & dosage
Double-Blind Method
Internal medicine
medicine
Humans
Dosing
Progression-free survival
Adverse effect
Aged
Neoplasm Staging
business.industry
Clinical trial
030104 developmental biology
business
Zdroj: Journal of Clinical Oncology
Lebbé, C, Meyer, N, Mortier, L, Marquez-Rodas, I, Robert, C, Rutkowski, P, Menzies, A M, Eigentler, T, Ascierto, P A, Smylie, M, Schadendorf, D, Ajaz, M, Svane, I M, Gonzalez, R, Rollin, L, Lord-Bessen, J, Saci, A, Grigoryeva, E & Pigozzo, J 2019, ' Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma : Results From the Phase IIIb/IV CheckMate 511 Trial ', Journal of Clinical Oncology, vol. 37, no. 11, pp. 867-875 . https://doi.org/10.1200/JCO.18.01998
ISSN: 1527-7755
DOI: 10.1200/JCO.18.01998
Popis: PURPOSE Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination. PATIENTS AND METHODS Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points. RESULTS At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group. CONCLUSION The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.
Databáze: OpenAIRE
Externí odkaz: