Durable Responses With Nivolumab in Previously Treated Advanced Renal Cell Carcinoma
In a phase I cohort-expansion study reported in the Journal of Clinical Oncology, McDermott et al found that nivolumab (Opdivo) produced durable responses in patients with previously treated advanced renal cell carcinoma. Responses continued after nivolumab discontinuation in some patients.
Study Details
In the study, 34 patients enrolled between 2008 and 2012 were treated with intravenous nivolumab 1 mg/kg (n = 18) or 10 mg/kg (n = 16) in an outpatient setting once every 2 weeks for up to 96 weeks and were observed for survival and duration of response. Patients had a median age of 58 years (range = 35–74 years), 76% were male, Eastern Cooperative Oncology Group performance status was 0 and 1 in 50% each, and 71% had two or more prior treatment regimens. Prior therapies included surgery in 94%; antiangiogenic agents in 71%; hormonal, immunologic, or biologic treatment in 71%; chemotherapy in 56%; mTOR inhibitor therapy in 32%; and radiotherapy in 29%. Lesions included bone in 29%, liver in 27%, lung in 88%, lymph nodes in 82%, and any visceral site in 88%.
Responses and Survival
Objective response on RECIST criteria was observed in 10 patients (29%), with a median response duration of 12.9 months. Nine additional patients (27%) had stable disease for ≥ 24 weeks. Another three patients (9%) had unconventional immune-related responses consisting of persistent reduction in target lesions in the presence of new lesions and regression after initial disease progression. In total, 20 (63%) of 32 evaluable patients exhibited some tumor shrinkage. Three of five patients who stopped treatment during response continued to have response for ≥ 45 weeks.
Median overall survival in all patients was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively.
Adverse Events
Grade 3 or 4 treatment-related adverse events occurred in 18% of patients, with the most common being hypophosphatemia (6%), pruritus (3%), and elevated alkaline phosphatase (3%). All of these adverse events were reversible. Management of immune-mediated adverse events with systemic glucocorticoids or other immunosuppressive agents was required in seven patients (21%); two resumed nivolumab within 15 days of occurrence, and the others discontinued therapy.
The investigators concluded: “Patients with advanced treatment-refractory [renal cell carcinoma] 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 [renal cell carcinoma].”
David F. McDermott, MD, of Beth Israel Deaconess Medical Center, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by Bristol-Myers Squibb, Ono Pharmaceutical, and the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
