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Lenvatinib and pembrolizumabor everolimus combinationin the treatment of renal cell carcinoma

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eMediNexus    27 April 2021

Lenvatinib combined with pembrolizumab or everolimus has demonstrated efficacy against advanced renal cell carcinoma. However, it is unclear whether efficacy of the combination is better compared with that of sunitinib. 

In a phase 3 trial, patients with advanced renal cell carcinoma and no previous systemic therapy were randomly assigned (in a1:1:1 ratio) to be given Lenvatinib (20 mg orally once daily) and pembrolizumab (200 mg intravenously once every 3 weeks), Lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily) or sunitinib (50 mg orally once daily, alternating 4 weeks getting treatment and 2 weeks without treatment). The results of the study showed that progression-free survival was more with Lenvatinib and pembrolizumab combination compared with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with Lenvatinib and everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). It was also seen that grade 3 or higher adverse events occurring in at least 105 of the patients in any group included hypertension, diarrhoea, and increased lipase levels. 

Based on the results of the phase 3 clinical studies, the authors concluded that Lenvatinib and pembrolizumab combination was linked with significantly longer progression-free survival and overall survival compared with treatment with sunitinib only. 

Reference: Motzer R, Alekseev B, Rha S-Y, Porta C, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma The New England Journal of medicine. 2021; 384: 1289-1300. 

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