PURPOSE: Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors.
We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts.
PATIENTS AND METHODS: A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation.
RESULTS: Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible.
CONCLUSION: Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.
Written by:
McDermott DF, Drake CG, Sznol M, Choueiri TK, Powderly JD, Smith DC, Brahmer JR, Carvajal RD, Hammers HJ, Puzanov I, Hodi FS, Kluger HM, Topalian SL, Pardoll DM, Wigginton JM, Kollia GD, Gupta A, McDonald D, Sankar V, Sosman JA, Atkins MB. Are you the author?
Beth Israel Deaconess Medical Center; Dana-Farber Cancer Institute/Brigham and Women's Hospital; Dana-Farber Cancer Institute, Boston, MA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Carolina BioOncology Institute, Huntersville, NC; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Memorial Sloan-Kettering Cancer Center, New York, NY; Bristol-Myers Squibb, Princeton, NJ; Vanderbilt-Ingram Cancer Center, Nashville, TN; Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC.
Reference: J Clin Oncol. 2015 Mar 30. pii: JCO.2014.58.1041.
doi: 10.1200/JCO.2014.58.1041
PubMed Abstract
PMID: 25800770