Prognostic impact of lenvatinib dose intensity in previously untreated patients with advanced renal cell carcinoma receiving lenvatinib plus pembrolizumab

BACKGROUND: Lenvatinib plus pembrolizumab is the standard of care as first-line systemic therapy for advanced renal cell carcinoma (RCC). However, the prognostic impact of the relative dose intensity (RDI) of lenvatinib remains unclear. METHODS: Clinical data from 54 patients with advanced RCC who received lenvatinib plus pembrolizumab as first-line therapy were retrospectively evaluated. The RDI of lenvatinib within the initial 3 months (3m-RDI) was calculated, and tumor response and survival were compared according to 3m-RDI. RESULT: The 3m-RDI threshold was set at 70%, which was significantly associated with objective response during treatment. Patients with a high 3m-RDI (≥70%) had a higher objective response rate (ORR) than those with a low 3m-RDI (<70%) (69% vs. 36%, P = .014).Multivariable analysis identified 3m-RDI ≥70% as an independent predictor of higher ORR (odds ratio: 5.25, 95% CI: 1.55-20.36, P = .007). Among patients with synchronous metastasis (n = 24), patients with a high 3m-RDI had higher ORR (62% vs. 18%, P = .028) and longer progression-free survival (median: not reached vs. 4.8 months, P = .035) than those with a low 3m-RDI. CONCLUSIONS: Lenvatinib with 3m-RDI ≥70% may be a useful early treatment-related marker associated with clinical outcomes during first-line lenvatinib plus pembrolizumab for advanced RCC.