• Hussein A Tawbi, Peter A Forsyth, Alain Algazi, Omid Hamid, F Stephen Hodi, Stergios J Moschos, Nikhil I Khushalani, Karl Lewis, Christopher D Lao, Michael A Postow, Michael B Atkins, Marc S Ernstoff, David A Reardon, Igor Puzanov, Ragini R Kudchadkar, Reena P Thomas, Ahmad Tarhini, Anna C Pavlick, Joel Jiang, Alexandre Avila, Sheena Demelo, and Kim Margolin.
• From the University of Texas M.D. Anderson Cancer Center, Houston (H.A.T.); Moffitt Cancer Center and Research Institute, Tampa, FL (P.A.F., N.I.K.); University of California-San Francisco, San Francisco (A. Algazi), the Angeles Clinic and Research Institute, Los Angeles (O.H.), Stanford University Hospital, Palo Alto (R.P.T.), and the Department of Medical Oncology, City of Hope, Duarte (K.M.) - all in California; Dana-Farber Cancer Institute, Boston (F.S.H., D.A.R.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (S.J.M.); University of Colorado Comprehensive Cancer Center, Aurora (K.L.); University of Michigan, Ann Arbor (C.D.L.); Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (M.A.P.), Roswell Park Cancer Institute, Buffalo (M.S.E., I.P.), and New York University, Lake Success (A.C.P.) - all in New York; Georgetown-Lombardi Comprehensive Cancer Center, Washington DC (M.B.A.); Winship Cancer Institute of Emory University, Atlanta (R.R.K.); University of Pittsburgh Medical Center, Pittsburgh (A.T.); Bristol-Myers Squibb, Princeton, NJ (J.J., A. Avila, S.D.); and Cleveland Clinic-Taussig Cancer Institute, Cleveland (A.T.).
• N. Engl. J. Med. 2018 Aug 23; 379 (8): 722730722-730.

BackgroundBrain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases.MethodsIn this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response.ResultsAmong 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56% (95% CI, 46 to 67). Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases.ConclusionsNivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. (Funded by Bristol-Myers Squibb and the National Cancer Institute; CheckMate 204 ClinicalTrials.gov number, NCT02320058 .).

31 keywords...

hide…