1386O_PR - Risk of incremental toxicities and associated costs of new anticancer drugs: A meta-analysis

Date 28 September 2014
Event ESMO 2014
Session Public health and health economics
Topics Complications of Treatment
Bioethics, Legal, and Economic Issues
Presenter Saroj Niraula
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors S. Niraula1, E. Amir2, B. Seruga3, F. Vera-Badillo4, A. Ocana5, I.F. Tannock4
  • 1Medical Oncology And Hematology, CancerCare Manitoba MacCharles, R3E 0V9 - Winnipeg/CA
  • 2Medical Oncology, Princess Margaret Hospital, Toronto/CA
  • 3Dept. Of Medical Oncology, Institute of Oncology LjubljanaUKC Ljubljana, SI-1000 - Ljubljana/SI
  • 4Dept Of Medical Oncology, Princess Margaret Hospital, M5G 2M9 - Toronto/CA
  • 5Medical Oncology, Albacete University Hospital, na - Albacete/ES




To quantify the frequency of serious toxicities caused by new anticancer drugs, and incremental costs associated with their management, according to the type of anticancer drugs.


We identified anticancer drugs approved by the United States Food and Drug Administration during 2000-2011, and pivotal trials supporting their registration. Twelve frequent, grade III-IV adverse event (AEs) were weighted and pooled in a meta-analysis to obtain both relative and absolute excess risk in experimental groups compared to the control groups of the registration trials. Estimates of incremental drug prices, and costs for management of AEs were calculated according to types of new agents based on (1) target-specificity of the new drugs and (2) activity of comparator groups used in the pivotal trials. Costs were derived from pharmacy "red book" and literature, adjusted for inflation to reflect 2014 dollar value.


We identified 41 studies (27,500 patients) involving 19 experimental drugs. Agents directed against a specific molecular target on cancer cells (i.e., predictive biomarker) had a lower incidence of grade III-IV toxicities than the controls (median relative risk [RR] = 0.7, p = 0.2), whereas less-specific targeted agents, including angiogenesis inhibitors (median RR = 3.4, p < 0.001), and chemotherapeutic agents (median RR = 1.6, p < 0.01) were more toxic. Risk was increased regardless of whether the control arm contained active treatment (RR = 2.1, p < 0.001) or not (RR = 3.0, p < 0.001). Median incremental drug-price for experimental agents was $6000/patient/month. Median cost of managing AEs was decreased in the experimental arm compared to the control for specifically targeted agents but this was persistently higher than controls across all 12 AEs for less-specific targeted agents and chemotherapy. Sensitivity analysis performed using broader hypothetical range strengthened the findings.


Newly approved anticancer drugs are associated with increased toxicity and management of toxicity leads to an increase in overall cost of treatment except when agents with a specific molecular target on cancer cells are used. Adopting policy to encourage development of biomarker-driven drugs is encouraged. Frequency of toxicity and associated costs are likely higher in less selected patients treated in general oncologic practice.


All authors have declared no conflicts of interest.