Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma

The CLEAR randomized clinical trial investigated lenvatinib as an alternative to sunitinib in the setting of advanced renal cell carcinoma. For the Phase III investigation, researchers worked with a sample of 1,069 patients with no history of systemic therapy. In all, 355 received lenvatinib plus pembrolizumab, 357 received lenvatinib plus everolimus, and 357 received sunitinib. The primary outcome was progression-free survival, which was measured in the treatment arms at 23.9 months, 14.7 months, and 9.2 months, respectively. The study also assessed overall survival and safety, finding that patients who received lenvatinib plus everolimus lived no longer than those who received sunitinib. Lenvatinib plus pembrolizumab, however, was associated not only with longer progression-free survival compared with sunitinib, but longer duration of overall survival. Participants who received either form of lenvatinib combination therapy suffered more adverse events rated grade 3 or higher compared with sunitinib recipients.