1. Disease-free survival in the placebo group was 50.7 months and was never reached in the intervention group; however, there were no significant differences.
2. 38% of patients in the intervention group reported grade 3-5 adverse events versus 10% in the placebo group which led to a greater proportion of treatment discontinuations in the former.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Nephrectomy is currently the standard of care for patients with localized renal cell carcinoma (RCC). However, despite resection of the tumor, up to 40% of patients are known to relapse. Immune checkpoint inhibitors, such as nivolumab and ipilimumab, may effectively target cancerous cells although little has been studied to date in this subset of patients. This randomized controlled trial aimed to compare the safety and efficacy of nivolumab plus ipilimumab versus placebo among adults with non-metastatic RCC following nephrectomy. The primary endpoint was disease-free survival while key secondary endpoints included overall survival, safety, and tolerability. According to study results, nivolumab plus ipilimumab did not improve disease-free survival and, in fact, resulted in greater adverse events compared to the placebo. Although this study was well done, it did not evaluate the effect of either nivolumab or ipilimumab independently to see if the reported adverse events could be attributed to one drug more than the other.
Click to read the study in The Lancet
Relevant Reading: Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma
In-depth [randomized-controlled trial]: Between Aug 28, 2017, and Mar 16, 2021, 1153 patients were assessed for eligibility across 145 centers in 20 countries. Included were patients ≥ 18 years old with localized histology-confirmed RCC, no distant metastasis post-nephrectomy, pathological T2a to pT3 staging, and Eastern Cooperative Oncology Group (ECOG) status ≤ 1. Altogether, 816 patients (405 to nivolumab plus ipilimumab and 411 to placebo) were included in the final analysis. The primary endpoint of disease-free survival was 50.7 months in placebo but was not attained in the intervention group (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.71-1.19, p=0.53). Regarding safety profiles, more patients in the intervention group (38%) reported grade 3-5 adverse events versus placebo (10%). There were 4 fatalities in the intervention group but none in the placebo group. Findings from this study suggest that treatment with nivolumab plus ipilimumab does not improve survival in patients with localized RCC and is associated with more adverse events.
Image: PD
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