Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial
Howard Gurney,
Thomas Powles,
Laurence Albiges,
Camillo Porta,
Toni K Choueiri,
Marc-Oliver Grimm,
Elizabeth R Plimack,
Brian I Rini,
Saby George,
Robert J Motzer,
Frede Donskov,
Philippe Barthélémy,
Christian K Kollmannsberger,
Yoshihiko Tomita,
M Brent McHenry,
Shruti Shally Saggi,
Nizar M Tannir,
Mauricio Burotto,
Daniel Castellano
Affiliations
Howard Gurney
Department of Medical Oncology, Westmead Hospital, Sydney, New South Wales, Australia
Thomas Powles
Aff3 grid.4868.20000000121711133Barts Cancer InstituteQueen Mary University of London London UK
Laurence Albiges
Aff416 grid.14925.3b0000000122849388Department of Cancer MedicineGustave Roussy Cancer Campus, University of Paris Sud Villejuif Ile-de-France France
Camillo Porta
9 Biomedical Sciences and Human Oncology, Università degli Studi di Bari Aldo Moro, Bari, Italy
Toni K Choueiri
Department of Medical Oncology, Dana-Farber Cancer Institute, The Lank Center for Genitourinary Oncology, Boston, Massachusetts, USA
Marc-Oliver Grimm
Aff2 grid.275559.90000000085176224Department of UrologyUniversity Hospital of Jena Jena Germany
Elizabeth R Plimack
Aff11 grid.412530.10000000404566466Department of Medical OncologyFox Chase Cancer Center Philadelphia PA USA
Brian I Rini
Aff9 0000 0001 0675 4725grid.239578.2Lerner College of Medicine, Department of Hematology and OncologyCleveland Clinic Taussig Cancer Institute 44195 Cleveland OH USA
Saby George
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA
Robert J Motzer
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
Frede Donskov
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
Philippe Barthélémy
Department of Medical Oncology, Hôpitaux Universitaires de Strasbourg / ICANS, Strasbourg, France
Christian K Kollmannsberger
Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
Yoshihiko Tomita
Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
M Brent McHenry
Bristol Myers Squibb, Princeton, New Jersey, USA
Shruti Shally Saggi
Bristol Myers Squibb, Princeton, New Jersey, USA
Nizar M Tannir
Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA
Mauricio Burotto
Bradford Hill Clinical Research Center, Santiago, Chile
Daniel Castellano
Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain
Purpose To report updated analyses of the phase III CheckMate 214 trial with extended minimum follow-up assessing long-term outcomes with first-line nivolumab plus ipilimumab (NIVO+IPI) versus (vs) sunitinib (SUN) in patients with advanced renal cell carcinoma (aRCC).Methods Patients with aRCC with a clear cell component were stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk and randomised to NIVO (3 mg/kg) plus IPI (1 mg/kg) every three weeks ×4 doses, followed by NIVO (3 mg/kg) every two weeks; or SUN (50 mg) once per day ×4 weeks (6-week cycle). Efficacy endpoints included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) per independent radiology review committee in patients with intermediate/poor-risk disease (I/P; primary), intent-to-treat patients (ITT; secondary) and in patients with favourable-risk disease (FAV; exploratory).Results Overall, 1096 patients were randomised (ITT: NIVO+IPI, n=550, SUN, n=546; I/P: NIVO+IPI, n=425, SUN, n=422; FAV: NIVO+IPI, n=125, SUN, n=124). After 4 years minimum follow-up, OS (HR; 95% CI) remained superior with NIVO+IPI vs SUN in ITT (0.69; 0.59 to 0.81) and I/P patients (0.65; 0.54 to 0.78). Four-year PFS probabilities were 31.0% vs 17.3% (ITT) and 32.7% vs 12.3% (I/P), with NIVO+IPI vs SUN. ORR remained higher with NIVO+IPI vs SUN in ITT (39.1% vs 32.4%) and I/P (41.9% vs 26.8%) patients. In FAV patients, the HRs (95% CI) for OS and PFS were 0.93 (0.62 to 1.40) and 1.84 (1.29 to 2.62); ORR was lower with NIVO+IPI vs SUN. However, more patients in all risk groups achieved complete responses with NIVO+IPI: ITT (10.7% vs 2.6%), I/P (10.4% vs 1.4%) and FAV (12.0% vs 6.5%). Probability (95% CI) of response ≥4 years was higher with NIVO+IPI vs SUN (ITT, 59% (0.51 to 0.66) vs 30% (0.21 to 0.39); I/P, 59% (0.50 to 0.67) vs 24% (0.14 to 0.36); and FAV, 60% (0.41 to 0.75) vs 38% (0.22 to 0.54)) regardless of risk category. Safety remained favourable with NIVO+IPI vs SUN.Conclusion After long-term follow-up, NIVO+IPI continues to demonstrate durable efficacy benefits vs SUN, with manageable safety.Trial registration details ClinicalTrials.gov identifier: NCT02231749.
