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Combining the multi-kinase inhibitor lenvatinib with pembrolizumab more than doubled the time to progression compared with sunitinib in advanced clear-cell kidney cancer and improved survival, with 71% of patients responding.
Open-label phase 3 trial of 1,069 patients with untreated advanced clear-cell renal cell carcinoma randomised to lenvatinib plus pembrolizumab, lenvatinib plus everolimus, or sunitinib. Primary endpoint was PFS by independent review.
Median PFS was 23.9 vs 9.2 months (HR 0.39) for lenvatinib plus pembrolizumab, with OS HR 0.66 and an objective response rate of 71.0% vs 36.1%. Alongside KEYNOTE-426 (axitinib plus pembrolizumab), CheckMate 9ER (cabozantinib plus nivolumab) and CheckMate 214 (nivolumab plus ipilimumab), it established immunotherapy-based combinations as universal first-line therapy for advanced kidney cancer.
Patients with newly diagnosed advanced clear-cell kidney cancer should receive an immunotherapy-based combination; lenvatinib plus pembrolizumab gives the highest response rate and longest PFS of the available options, at the cost of more side effects requiring dose adjustment. Sunitinib alone is no longer an appropriate standard. Choosing among the combinations depends on risk group, symptoms, comorbidity and the value placed on treatment-free survival, which favours nivolumab plus ipilimumab in intermediate and poor risk.
Shares Toni K. Choueiri, Clear cell renal cell carcinoma, Overall survival (OS), Merck & Co. (MSD).
Shares Lines of therapy, Objective response rate (ORR), Too many combinations to test, Progression-free survival (PFS).
Shares Clear cell renal cell carcinoma, Anti-angiogenic therapy, Merck & Co. (MSD), Renal cell carcinoma.
Shares Lines of therapy, Progression-free survival (PFS), Overall survival (OS), VEGF / VEGFR.
Shares Toni K. Choueiri, Clear cell renal cell carcinoma, Overall survival (OS), Merck & Co. (MSD).
Shares Lines of therapy, Too many combinations to test, Progression-free survival (PFS), Overall survival (OS).
Shares Toni K. Choueiri, Robert J. Motzer, Progression-free survival (PFS), Renal cell carcinoma.
Shares VEGF / VEGFR, Anti-angiogenic therapy, Renal cell carcinoma, PD-1.