Dr Robert J. Motzer on the survival benefit of pembrolizumab / lenvatinib in first-line CRC

Robert J. Motzer, MD, kidney cancer section chief, genitourinary oncology service; and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center, discusses the results of the CLEAR phase 3 trial, of which he was the first author. The study showed that first-line treatment with pembrolizumab (Keytruda) plus lenvatinib (Lenvima) reduced the risk of death by 34% compared to sunitinib (Sutent) in patients with advanced renal cell carcinoma.^{1, 2}

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

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

Median OS was not achieved in any of the 3 treatment arms; however, the data indicated that the endpoint was significantly longer in the lenvatinib and pembrolizumab arm than in the sunitinib arm (HR, 0.66; P = .005). Motzer noted that no OS benefit was seen in the lenvatinib and everolimus treatment arm compared to sunitinib alone (HR, 1.15; P = .3).

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

The 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 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