Nexavar — A Multikinase Inhibitor Approved for the Treatment of Patients With Advanced RCC*Proven efficacy in the largest phase III study for advanced RCCThe efficacy and safety of Nexavar was proven in the largest phase III, multicentre, randomised, double-blind, placebo-controlled trial conducted in advanced RCC. Nexavar was shown to significantly double progression-free survival (P<.000001; HR: 0.44; 95% CI, 0.35-0.55), vs placebo across all patient subsets.1,2 In a preplanned interim analysis, the rate of overall survival (OS) was longer with Nexavar than placebo with a hazard ratio of 0.72 based on 220 deaths (95% CI, 0.54-0.94).2 The analysis did not meet the prespecified criteria for statistical significance. However, in a preplanned placebo-censored analysis, excluding patients who crossed over to Nexavar, results showed a significant survival advantage (17.8 months median OS vs 14.3 months; HR: 0.78; 95% CI, 0.62-0.97; P=.0287).3 Nexavar was generally well tolerated with a predictable profile. The most common adverse events were diarrhoea, rash/desquamation, fatigue, hand-foot skin reaction, alopecia, and nausea/vomiting. Kinases are important anticancer targetsKinases are specialised proteins that function within intracellular communication networks known as signal transduction pathways.4 In cancer, preclinical studies have shown that these pathways are important in the development of tumour vasculature and in the proliferation of tumour cells, leading to tumour growth and metastases. Therefore, by blocking the kinases involved in these signalling pathways, tumour growth and proliferation may be controlled.5 Kinases are located on multiple levels of signalling pathways. Receptor tyrosine kinases are located upstream in the signalling pathway of tumour vasculature (e.g., VEGFR and PDGFR) and tumour cells (eg, KIT and FLT-3). Serine/threonine kinases are located downstream in the signalling pathway within the cells of tumours and tumour vasculature (eg, RAF/MEK/ERK).5 Multikinase inhibition is important to cancer treatmentMultikinase inhibition works at multiple levels of signalling pathways in tumour cells and tumour vasculature. For example, preclinical studies have shown that by providing upstream blockade of VEGF and PDGF receptors as well as downstream blockade of the RAF/MEK/ERK pathway, Nexavar simultaneously decreases both angiogenesis and tumour cell proliferation, which helps by blocking tumour growth.5 *Nexavar is indicated for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha- or interleukin-2-based therapy or are considered unsuitable for such therapy. Next: TARGET Phase III Clinical Trial Design and Results Term Explanation for term. |
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