Adding lenvatinib to pembrolizumab does not improve survival in advanced urothelial carcinoma

Results from the phase 3 LEAP-011 trial showed that the combination of lenvatinib and pembrolizumab induced comparable anti-tumour activity compared with placebo plus pembrolizumab as first-line therapy in patients with advanced urothelial carcinoma who were ineligible for platinum-based chemotherapy.

Pembrolizumab is an approved first-line therapy for patients with advanced urothelial carcinoma who are ineligible for platinum-based chemotherapy [1]. Lenvatinib, a multiple-receptor kinase inhibitor, has shown anti-tumour activity in several solid tumours [2]. When combined with pembrolizumab, lenvatinib showed promising early activity and manageable safety in previously treated patients with advanced urothelial carcinoma, regardless of PD-L1 status, in the phase 1b/2 KEYNOTE-146 trial [3].

The phase 3 LEAP-011 trial (NCT03898180) aimed to examine the combination of pembrolizumab plus lenvatinib in the first-line setting for patients with histologically-confirmed advanced or metastatic urothelial carcinoma who are ineligible for platinum-based chemotherapy. A total of 497 patients who were cisplatin-ineligible with tumours expressing PD-L1 (combined positive score ≥10) or were ineligible to receive platinum-based chemotherapy regardless of PD-L1 status were enrolled in LEAP-011. Participants were randomised 1:1 to receive pembrolizumab plus lenvatinib or pembrolizumab plus placebo. The dual primary endpoints were progression-free survival (PFS) and overall survival (OS). Dr Yohann Loriot (Institut Gustave Roussy, France) presented the results of LEAP-011 [4].

Median PFS was 4.5 months in the pembrolizumab/lenvatinib arm versus 4.0 months in the pembrolizumab/placebo arm (HR 0.90). Median OS was 11.8 months with pembrolizumab/lenvatinib versus 12.9 months with pembrolizumab/placebo (HR 1.14). The overall response rate was 33.1% versus 28.9%, respectively.

Treatment-related adverse events occurred in 87.6% of pembrolizumab/lenvatinib-treated patients arm and in 69.0% of pembrolizumab/placebo-treated patients.

Based on these results, the data-monitoring committee recommended to stop further enrolment of patients in LEAP-011. “The benefit/risk ratio for adding lenvatinib to pembrolizumab was not considered positive in patients with advanced urothelial carcinoma who are platinum-ineligible,” concluded Dr Loriot. “Therefore, pembrolizumab monotherapy remains the standard of care as first-line therapy in these patients.”

1. Vuky J, et al. J Clin Oncol. 2020;38:2658–2666.
2. Zschäbitz S, et al. Recent Results Cancer Res. 2018;211:187–198.
3. Taylor MH, et al. J Clin Oncol. 2020;38:1154–1163.
4. Loriot, Y, et al. First-line pembrolizumab (pembro) with or without lenvatinib (lenva) in patients with advanced urothelial carcinoma (LEAP-011): A phase 3, randomized, double-blind study. Abstract 432, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 202217 May 2024