Risk of Incremental Toxicities and Associated Costs of New Anticancer Drugs: A Meta-Analysis

Purpose There are increasing reports of rare but serious toxicities caused by new anticancer drugs, and there are costs associated with their management. Methods We identified anticancer drugs approved by the US Food and Drug Administration from 2000 to 2011 and pivotal trials supporting their registration. Twelve frequent grade 3 to 4 adverse event (AEs) were weighted and pooled in a meta-analysis. Estimates of incremental drug prices and incremental costs for management of AEs were calculated according to type of new agent based on target specificity. Results We identified 41 studies comprising 27,539 patients and evaluating 19 experimental drugs. Agents directed against a specific molecular target on cancer cells had a lower incidence of grade 3 to 4 toxicities compared with controls (median risk ratio [RR], 0.67; P = .22), whereas less-specific targeted agents, including angiogenesis inhibitors (median RR, 3.39; P < .001) and chemotherapeutic agents (median RR, 1.73; P < .001), were more toxic. Risk was increased regardless of whether the control arm contained active treatment (RR, 2.11; P < .001) or not (RR, 3.02; P < .001). Median incremental drug price for experimental agents was $6,000 per patient per month. Median cost of managing toxicity was low compared with drug costs but higher than controls for treatment with less-specific targeted agents and chemotherapies. Conclusion Newly approved anticancer drugs are associated with increased toxicity, except for agents with a specific molecular target on cancer cells. Management of toxicity leads to a small increase in overall cost of treatment. Frequency of toxicity and associated costs are likely higher in less-selected patients treated in general oncologic practice. Development of biomarker-driven agents should be encouraged.