Dr. Robert J. Motzer on pembrolizumab/lenvatinib survival benefit in frontline RCC


Motzer highlights the overall survival benefit achieved with the combination of the PD-1 inhibitor and the multikinase inhibitor versus standard sunitinib in the phase 3 CLEAR trial.

Robert J. Motzer, MD, the Kidney Cancer Section Head, Genitourinary Oncology Service; and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center, discusses findings from the phase 3 CLEAR trial, on which he was the first author. The study showed that frontline therapy with pembrolizumab (Keytruda) plus lenvatinib (Lenvima) reduced the risk of death by 34% versus sunitinib (Sutent) in patients with advanced renal cell carcinoma.1,2

The combination of the anti–PD-1 immunotherapy and the multikinase inhibitor also improved progression-free survival (PFS) and response compared with sunitinib. The results of the trial, , also showed that combining lenvatinib with the mTOR inhibitor everolimus (Afinitor) improved PFS and objective response rate (ORR) but not OS versus sunitinib in this setting.

The median PFS with lenvatinib and pembrolizumab was 23.9 months compared to 9.2 months with single-agent sunitinib (HR, 0.39; < .001). The lenvatinib plus everolimus treatment arm achieved a median PFS of 14.7 months compared to the 9.2 months in the sunitinib arm (HR, 0.65; < .001).

A median OS was not reached in any of the 3 treatment arms; however, the data indicated the end point was significantly longer in the lenvatinib and pembrolizumab arm compared to the sunitinib arm (HR, 0.66; = .005). Motzer noted that there was no observed OS benefit in the lenvatinib and everolimus treatment arm over sunitinib alone (HR, 1.15; = .3).

ORR was higher in both the lenvatinib plus pembrolizumab (71%) and lenvatinib plus everolimus (53.5%) treatment arms compared to sunitinib (36.1%).


1. Motzer RJ, Porta C, Eto M, et al. Phase 3 trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) monotherapy as a first-line treatment for patients (pts) with advanced renal cell carcinoma (RCC) (CLEAR study). J Clin Oncol. 2021; 39(suppl6):269. doi: 10.1200/JCO.2021.39.6_suppl.269

2. Motzer RJ, Alekseev B, Rha S.-Y., et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. Published online February 13, 2021. N Engl J Med. doi: 10.1056/NEJMoa2035716

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