Robert J. Motzer, MD, Head of Renal Cancer Division, Genitourinary Oncology Service; and Jack and Dorothy Byrne Chair in Clinical Oncology at the Sloan Kettering Cancer Memory Center, discussing results from a CLEAR level 3 trial, of which he was the first author. The study showed that face treatment with pembrolizumab (Keytruda) plus lenvatinib (Lenvima) reduced the risk of death by 34% against 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 survival without improvement (PFS) and response compared with sunitinib. The results of the experiment also showed that lenvatinib combined with the mTOR inhibitor everolimus (Afinitor) combined PFS and target response rate (ORR) but not OS against sunitinib in this setting.
The median PFS with lenvatinib and pembrolizumab was 23.9 months compared with 9.2 months with single-agent sunitinib (HR, 0.39; P. <.001). The treatment arm lenvatinib plus everolimus achieved a median PFS of 14.7 months compared with the 9.2 months in the sunitinib arm (HR, 0.65; P. <.001).
Medium OS was not reached in any of the 3 handling arms; however, the data showed that the termination point was significantly longer in the lenvatinib and pembrolizumab arm compared to the sunitinib arm (HR, 0.66; P. = .005). Motzer noted that OS benefit was not seen in the manipulative arm lenvatinib and everolimus over sunitinib alone (HR, 1.15; P. = .3).
ORR was higher in both the lenvatinib plus pembrolizumab treatment arms (71%) and lenvatinib plus everolimus (53.5%) compared with sunitinib (36.1%).
References
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 (supply6): 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