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The explosion of clinical trials involving new targeted agents has raised hopes for more-effective and less-toxic treatment modalities. Unfortunately, this story has proven more complicated than expected. Consider sorafenib (Nexavar), an inhibitor of tyrosine kinases that are involved in tumor progression and angiogenesis. In pivotal trials that led to the FDA’s approval of sorafenib for metastatic renal cell carcinoma (N Engl J Med 2007; 356:125) and advanced hepatocellular carcinoma (J Clin Oncol 2007; 25:18S LBA1), the agent significantly prolonged progression-free survival and overall survival. However, sorafenib had minimal effects on objective-response rates, suggesting that its greatest benefit might be disease stabilization rather t…