pazopanib + lapatinib

Combination of two oral small-molecule tyrosine kinase inhibitors investigated for solid tumors. Pazopanib is a multi-targeted angiogenesis inhibitor of vascular endothelial growth factor receptors (VEGFR-1/2/3), platelet-derived growth factor receptors (PDGFR-α/β), and KIT; lapatinib is a dual epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) inhibitor. Clinical studies explored additive or synergistic antitumor activity by concurrently inhibiting tumor cell growth signaling and tumor angiogenesis. Phase I/II trials identified feasible daily oral dosing regimens but showed increased gastrointestinal and hepatic toxicity with the combination and no progression-free survival advantage over lapatinib alone in HER2-positive inflammatory breast cancer; in cervical cancer, an interim analysis led to early discontinuation of the combination arm for futility compared with lapatinib, while pazopanib monotherapy improved outcomes over lapatinib. Recommended phase II doses evaluated included pazopanib 800 mg plus lapatinib 1,500 mg daily, and a lower-dose regimen of pazopanib 400 mg plus lapatinib 1,000 mg daily used for tolerability in some cohorts.[3][2][7][1]

Other names

pazopanib plus lapatinib