Results from the phase 3 CLEAR study, presented at the virtual American Society of Clinical Oncology Genitourinary Cancers Symposium over the weekend, showed that lenvatinib used in combination with either pembrolizumab or everolimus resulted in improved survival and tumour shrinkage compared to sunitinib when used as a first-line treatment for patients with advanced renal cell carcinoma (RCC).

The combination of lenvatinib and everolimus has been shown to improve progression-free survival compared to everolimus in previously treated patients with advanced RCC. Also, results from a recent phase 1b/2 study of lenvatinib plus pembrolizumab showed anti-cancer activity in advanced RCC patients who had already been treated. In the current study, researchers aimed to assess the safety and efficacy of lenvatinib plus pembrolizumab, as well as lenvatinib plus everolimus, versus sunitinib in untreated patients with advanced RCC.

There were 1069 patients in the study, who were randomly allocated to 3 treatment groups: lenvatinib plus pembrolizumab, lenvatinib plus everolimus, or sunitinib. For the patients who were treated with lenvatinib and pembrolizumab, progression-free survival was significantly extended to 23.9 months compared to 9.2 months for sunitinib. Lenvatinib plus everolimus also improved progression-free survival to 14.7 months compared to sunitinib. The overall survival endpoint was not reached during the study, but the data indicate overall survival to be significantly longer in the lenvatinib and pembrolizumab arm compared to the sunitinib arm. Tumour shrinkage (response rate) was higher in both the lenvatinib plus pembrolizumab (71%) and lenvatinib plus everolimus (53.5%) groups compared to sunitinib (36.1%), with a high complete response rate of 16.1% with lenvatinib plus pembrolizumab.

Nearly all patients in the study had side effects to treatment. Patients in the combination treatment groups were more likely to have a dose reduction due to side effects (around two thirds of patients) than patients in the sunitinib group (around half of patients). However, the safety of each combination treatment was not unexpected and the side effects were manageable.

In conclusion, “These results support lenvatinib plus pembrolizumab as a potential first-line treatment for patients with advanced RCC,” said Dr Motzer from Memorial Sloan Kettering Cancer Center in the USA.

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