New Agents That Improve Efficacy Can Also Increase Morbidity and Treatment-related Mortality

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Newly approved anticancer drugs that lead to improvements in efficacy can also lead to increased morbidity and treatment-related mortality, according to a study in the Journal of Clinical Oncology. The investigators conducted a meta-analysis of 38 randomized controlled trials evaluating agents approved by the FDA for the treatment of solid tumors. “Our analysis shows that most newly approved anticancer drugs are associated with increased odds of toxic death, treatment discontinuation, and severe adverse events compared with the standard treatment received by controls,” the authors reported.

Treatment-related toxicities from these new agents are even more likely to occur in clinical practice than in clinical trials because patients seen in clinical trials are “generally selected for good performance status and few comorbidities,” the authors pointed out. “It is therefore not possible to predict the real-life outcomes and extent of such toxicities with the data generated by [randomized controlled trials].”

Use of new targeted agents and chemotherapy among less selected patients in general oncologic practice should take into consideration the health status of the individual patient. The investigators support large population-based outcome studies to quantify real-life efficacy and toxicity and identify variations among different populations.

“Our analysis showed no correlation between the end points of efficacy and toxicity,” the investigators reported. “Efficacy of treatment is determined by a variety of disease-related factors such as the intrinsic sensitivity of tumor cells, which in turn depends on the molecular properties of the tumor and the tumor microenvironment. Toxicity is dependent more on drug metabolism and clearance and is influenced by biologic characteristics of the host including performance status, comorbidities, drug-metabolizing enzymes, organ function, and concurrent medications. Therefore, it is not surprising that, in general, efficacy and toxicity of a drug are independent of each other. Although there have been reports relating toxicities of some targeted agents to their efficacy, this is likely to occur when inhibition of the same targets is responsible for producing both efficacy and toxicity.” ■

Niraula S, et al: J Clin Oncol. July 16, 2012 (early release online).




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