Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab.

Abstract

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.

• Authors: David F McDermott, Charles G Drake, Mario Sznol, Toni K Choueiri, John D Powderly, David C Smith, Julie R Brahmer, Richard D Carvajal, Hans J Hammers, Igor Puzanov, F Stephen Hodi, Harriet M Kluger, Suzanne L Topalian, Drew M Pardoll, Jon M Wigginton, Georgia D Kollia, Ashok Gupta, Dan McDonald, Vindira Sankar, Jeffrey A Sosman, Michael B Atkins
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 18 Pg. 2013-20 (Jun 20 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 25800770 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Nivolumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage)
• Antineoplastic Agents (administration & dosage)
• Carcinoma, Renal Cell (drug therapy, mortality)
• Cohort Studies
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Female
• Humans
• Kidney Neoplasms (drug therapy, mortality)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Nivolumab
• Patient Safety
• Programmed Cell Death 1 Receptor (immunology)
• Time Factors
• Treatment Outcome