CLEAR: Lenvatinib, Pembrolizumab Showed Continued Benefit in Advanced RCC

By Leah Lawrence - Last Updated: September 16, 2022

Combination treatment with first-line lenvatinib plus pembrolizumab continued to show a clinically meaningful benefit at 2 years compared with sunitinib in patients with advanced renal cell carcinoma (RCC).

These updated results of the CLEAR study were presented by Camillo G. Porta, of University of Bari, Italy, at the ESMO Congress 2022.

The trial randomly assigned patients with advanced RCC and no prior therapy 1:1:1 to lenvatinib 20 mg plus pembrolizumab 200 mg every 3 weeks, lenvatinib 18 mg plus everolimus, or sunitinib.

Initial results of the phase-3 study, published in The New England Journal of Medicine, showed a significant improvement in progression-free survival and improved overall response rate with lenvatinib plus pembrolizumab compared with sunitinib in the first-line setting.

With 7 additional months of follow-up, median survival follow-up is now 33.7 months for patients assigned lenvatinib plus pembrolizumab and 33.4 months for sunitinib. Median progression-free survival continued to be higher for the combination at 23.3 months compared with 9.2 months for sunitinib (hazard ratio=0.42; 95% CI, 0.34-0.52).

Similarly, the overall response rate with lenvatinib plus pembrolizumab was 71.0% compared with 36.1% for sunitinib. Duration of response was also longer in the combination arm (26.0 vs. 14.7 months). Porta pointed out that 17.2% of patients assigned the combination had a complete response, which was “the highest percentage of complete response ever observed in kidney cancer.”

Continued improvements in overall survival with lenvatinib plus pembrolizumab were also observed, Porta said. At 2 years, the overall survival rate was 80.2% compared with 69.7% for sunitinib.

“Unfortunately, the low number of patients with good risk prevented us from clearly define the activity of this combination in good-risk patients,” Porta said.

Patients who completed 2 years of pembrolizumab had a 36-month overall survival rate of 94.5%.



ESMO Congress 2022 – 1449MO – Updated efficacy of lenvatinib (LEN) + pembrolizumab (PEMBRO) vs sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in the CLEAR study