Literature
Clinical Pearls & Morning Reports
Published April 4, 2018
How does the combination of nivolumab plus ipilimumab compare to sunitinib for previously untreated advanced renal-cell carcinoma?
Combination therapy with nivolumab plus ipilimumab has shown promising efficacy in multiple tumor types, resulting in higher rates of response than either agent alone, and is approved for the treatment of advanced melanoma. Motzer et al. conducted the phase 3 CheckMate 214 trial of nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma. Read the latest NEJM Original Article here.
Clinical Pearls
Q: What is the present role of sunitinib in the treatment of renal-cell carcinoma?
A: Sunitinib, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, is a standard of care for first-line treatment of advanced renal-cell carcinoma.
Q: How does the combination of nivolumab plus ipilimumab compare to sunitinib for previously untreated advanced renal-cell carcinoma?
A: Three quarters of the patients with advanced renal-cell carcinoma have intermediate- or poor-risk clinical features. In the trial by Motzer et al., the coprimary end points were the objective response rate, progression-free survival, and overall survival among intermediate- and poor-risk patients. Two of the three coprimary end points were met; among intermediate- and poor-risk patients, the risk of death was 37% lower with nivolumab plus ipilimumab than with sunitinib, and the objective response rate was higher with nivolumab plus ipilimumab. Progression-free survival among intermediate- and poor-risk patients was longer with nivolumab plus ipilimumab than with sunitinib but did not meet the prespecified boundary for statistical significance.
Morning Report Questions
Q: Among patients with advanced renal-cell carcinoma, is the combination of nivolumab plus ipilimumab effective across all risk groups and tumor PD-L1 expression levels?
A: In the CheckMate 214 trial, the favorable-risk group had a higher objective response rate and longer progression-free survival with sunitinib than with nivolumab plus ipilimumab; these differences did not translate into a significant survival advantage. Longer progression-free survival with nivolumab plus ipilimumab than with sunitinib was observed among patients with 1% or greater PD-L1 expression but not among those with less than 1% PD-L1 expression. In contrast, longer overall survival and a higher objective response rate were observed with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients across tumor PD-L1 expression levels, although the magnitude of benefit was higher in the population with 1% or greater PD-L1 expression.
Q: Were any new safety concerns raised regarding the use of nivolumab plus ipilimumab in the CheckMate 214 trial?
A: The safety profile of nivolumab plus ipilimumab was consistent with that in previous studies in multiple tumor types, including advanced renal-cell carcinoma, with a lower incidence of grade 3 and 4 treatment-related adverse events than observed with sunitinib. The frequencies of treatment-related gastrointestinal, skin, and hepatic adverse events were lower than those seen in a trial involving patients with melanoma, in which a higher dose of ipilimumab (3 mg per kilogram) and a lower dose of nivolumab (1 mg per kilogram) were used. Patients reported better health-related quality of life with nivolumab plus ipilimumab than with sunitinib.