The combination of pembrolizumab and lenvatinib is FDA-approved for multiple solid tumors. It pairs anti-PD-1 checkpoint blockade with multi-kinase inhibition of VEGFR, FGFR, and RET to provide synergistic anti-tumor and anti-angiogenic activity.
FDA-approved for: Advanced RCC (first-line, in combination); Metastatic or advanced endometrial carcinoma that is not MSI-H or dMMR (following prior systemic therapy); Hepatocellular carcinoma (as first-line combination); Certain thyroid cancers (differentiated thyroid cancer after radioiodine failure).
RCC (first-line): Lenvatinib 20 mg orally once daily + Pembrolizumab 200 mg IV every 3 weeks (or 400 mg every 6 weeks).
Endometrial carcinoma: Lenvatinib 20 mg orally once daily + Pembrolizumab 200 mg IV every 3 weeks.
HCC (first-line): Lenvatinib 12 mg/day (≥60 kg) or 8 mg/day (<60 kg) orally once daily + Pembrolizumab 200 mg IV every 3 weeks.
Hypertension (72%), Fatigue (63%), Diarrhea (55%), Nausea (43%), Decreased appetite (41%), Hypothyroidism (57%), Weight loss (34%), Proteinuria (32%)
Adverse reaction frequencies reflect combination regimen data. Consult individual prescribing information for complete details.
Complementary dual-pathway blockade: Pembrolizumab blocks PD-1 on T cells, restoring anti-tumor immune responses by preventing ligand-mediated immunosuppression. Lenvatinib inhibits VEGFR 1–3, FGFR 1–4, PDGFR-α, RET, and KIT tyrosine kinases, reducing tumor angiogenesis, proliferation, and the immunosuppressive tumor microenvironment. Lenvatinib's anti-angiogenic activity may enhance T cell infiltration, amplifying pembrolizumab's effects.