Lenvatinib + pembrolizumab improves PFS in East Asian patients with advanced RCC

Lenvatinib + pembrolizumab combination regimen improves progression-free survival (PFS) compared with sunitinib in a subset of East Asian patients with advanced renal cell carcinoma (aRCC), a finding that was similar to that of the global population of the CLEAR* trial, according to a subanalysis presented at ASCO GU 2022.

“In the global population of the CLEAR trial, the safety profile of lenvatinib + pembrolizumab was considered manageable and generally consistent with the established profiles of each monotherapy,” said lead author Dr Sun Young Rha from Yonsei Cancer Center at Yonsei University Health System in Seoul, South Korea.

“The incidence of kidney cancer is increasing in Asian countries, [particularly in Japan and Korea, therefore,] … it is important to continue to examine the efficacy and tolerability of lenvatinib plus pembrolizumab in Asian populations,” she noted.

The subanalysis of the phase III CLEAR trial involved 75 and 65 East Asian patients with aRCC from Japan and Korea, respectively, who had no prior systemic therapy. Participants were given oral lenvatinib 20 mg once daily + intravenous pembrolizumab 200 mg every 3 weeks (n=42 [Japan] and n=33 [Korea], mean age 65 years) or sunitinib (n=31 [Japan] and 34 [Korea], mean age 61 years). [ASCO GU 2022, abstract 338]

East Asian patients treated with lenvatinib + pembrolizumab achieved a longer PFS compared with sunitinib (median, 22.1 vs 11.1 months; hazard ratio [HR], 0.38), similar to findings in the global population (HR, 0.39).

The median overall survival was not reached in both treatment arms (HR, 0.71). “However, this was limited [due to] small sample size and low number of events,” said Rha.

A higher objective response rate was observed among those on lenvatinib + pembrolizumab than those on sunitinib (65.3 percent vs 49.2 percent; odds ratio, 2.14), with a longer response duration (median, 20.3 vs 12.9 months).

Grade 3–5 treatment-emergent adverse events (TEAEs) occurred in 88.0 percent of patients on lenvatinib + pembrolizumab and 79.7 percent of patients on sunitinib in the East Asian population, and these rates were similar to that observed in the global population at 82.4 percent and 71.8 percent, respectively.

However, a higher incidence of hand-foot syndrome (66.7 percent vs 4.0 percent) and proteinuria (56.0 percent vs 7.7 percent) was observed among East Asian population than the global population treated with lenvatinib + pembrolizumab. “As expected, … these findings are consistent with prior trials of TKIs in East Asian populations,” said Rha.

Any TEAEs leading to treatment discontinuation were comparable between the lenvatinib + pembrolizumab and the sunitinib arms (16.0 percent vs 15.6 percent), with an increase in dose reduction for lenvatinib and sunitinib in the East Asian population, but it was consistent with the previous reports and considered manageable, noted Rha.

“[Overall,] efficacy results for patients in the East Asian subset of the CLEAR trial were generally consistent with the results of the global population and favoured lenvatinib + pembrolizumab over sunitinib,” said Rha.

Although there was an increase in the rate of dose reductions and certain TEAEs, the safety profile of lenvatinib + pembrolizumab in the East Asian subset was manageable and generally consistent with that of the global population.

“These data support the use of the combination of lenvatinib + pembrolizumab at the recommended starting dose with appropriate dose modifications for Asian patients to optimize efficacy and safety,” Rha added.