The US Food and Drug Administration (FDA) has granted approval to nivolumab (Opdivo) and ipilimumab (Yervoy) in combination for the first-line treatment of intermediate-risk or poor-risk patients with advanced renal cell carcinoma (RCC), which has previously been untreated.
The approval is based on the results from the CheckMate 214 clinical trial, which compared the nivolumab-ipilimumab combination with standard first-line treatment with sunitinib in patients with previously untreated advanced RCC. In this study, patients with intermediate- or poor-risk clear cell RCC responded better and survived longer with first-line treatment with the combination than with standard sunitinib treatment.
Efficacy was evaluated in 847 intermediate- or poor-risk patients, and showed statistically significant improvements in overall survival (OS) and objective response rate (ORR) for the 425 patients receiving the combination compared with those receiving sunitinib (422 patients). OS was not reached in the patients taking the combination compared with 25.9 months in patients receiving sunitinib. However, overall survival rates at 18 months were 75% vs 60% in favour of the ipilimumab-nivolumab combination.
A significantly higher proportion of patients responded to the combination therapy: the ORR was 41.6% for the combination versus 26.5% for sunitinib, and 9% of patients had a complete response with the combination vs 1% with sunitinib. The efficacy of the combination in favourable-risk patients with previously untreated RCC was not established.
Median progression-free survival (PFS) was longer with the combination, but this finding was not significant: 11.6 vs 8.4 months.
The most common adverse reactions (reported in at least 20% of patients treated with the combination) were fatigue, rash, diarrhoea, musculoskeletal pain, itchy skin, nausea, cough, fever, joint pain, and decreased appetite. The combination group also reported greater quality of life.
The recommended schedule and dose for this combination is nivolumab, 3 mg/kg, followed by ipilimumab, 1 mg/kg, on the same day every 3 weeks for 4 doses, then nivolumab, 240 mg, every 2 weeks or 480 mg every 4 weeks.
In England and Wales, the National Institute for Health and Care Excellence (NICE) is currently appraising the use of the ipilimumab-nivolumab combination for previously untreated patients with metastatic RCC. The appraisal committee meeting is taking place on 10th May 2018, and NICE guidance is expected to be published in October 2018. We will keep you updated on the progress of this appraisal.