On April 16, 2018, the FDA granted approval to treat frontline, intermediate or poor risk advanced renal cell carcinoma (RCC) with the combination of nivolumab (OPDIVO®) and ipilimumab (YERVOY®) . There are about 65,000 new cases of RCC in the United States (US) each year, and RCC accounts for about 15,000 deaths per year in the US . Standard frontline treatment for RCC includes anti-angiogenic treatment with sunitinib, a tyrosine kinase inhibitor (TKI) that targets several angiogenesis-promoting kinases . Unfortunately, most patients with advanced RCC eventually progress on therapy, thus there is an unmet need for treatments that can provide a durable response. Both nivolumab and ipilimumab are immune checkpoint inhibitors that can stimulate or enhance autonomous anti-tumor immune responses and have been found to produce durable responses in many tumor types. These agents work on different, but parallel, immune checkpoint pathways, and therefore may further enhance immune responses when used in combination .
The combination was approved to treat frontline, intermediate or poor risk advanced RCC based on the results of a randomized, open-label phase 3 trial, CheckMate 214, that compared the combination to standard sunitinib therapy (NCT02231749) . Patients were randomized 1:1 to receive nivolumab plus ipilimumab intravenously every 3 weeks for a total of four doses, followed by nivolumab every 2 weeks, or daily oral sunitinib for four weeks out of 6-week cycles. Patients receiving the nivolumab-ipilimumab combination experienced an improved overall survival rate at 18-months compared to those receiving sunitinib treatment, 75% vs 60%, respectively . Additionally, the overall response rate was improved in the nivolumab-ipilimumab arm, 42% vs. 27% as well . Remarkably, grade 3 or 4 adverse events occurred at a lower rate in the combination arm than the sunitinib arm with 46% vs. 65% of patients experiencing a grade 3 or 4 event, respectively . This approval provides another therapeutic option for patients with advanced RCC.
- OPDIVO (nivolumab) injection, for intravenous use Drugs@FDA: FDA Approved Drug Products [cited 2018 May 4]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125554s058lbl.pdf.
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- Motzer, R.J., et al., Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med, 2018. 378(14): p. 1277-1290.
- Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214). ClinicalTrials.gov [cited 2028 May 4]; Available from: https://clinicaltrials.gov/ct2/show/NCT02231749.