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Original Investigation
November 29, 2018

Cost-effectiveness of Maintenance Capecitabine and Bevacizumab for Metastatic Colorectal Cancer

Author Affiliations
  • 1Department of Surgery, University of Chicago, Chicago, Illinois
  • 2Department of Surgery, Medical College of Wisconsin, Milwaukee
  • 3Department of Surgery, University of Texas Rio Grande Valley, Edinburg
  • 4Department of Medicine, University of Chicago, Chicago, Illinois
JAMA Oncol. Published online November 29, 2018. doi:10.1001/jamaoncol.2018.5070
Key Points

Question  For metastatic colorectal cancer, what is the incremental cost-effectiveness of adding capecitabine and bevacizumab maintenance treatment after standard induction chemotherapy?

Findings  This economic evaluation study finds that compared with observation, capecitabine and bevacizumab maintenance therapy adds average per-patient benefits of 0.14 quality-adjusted life-years (QALYs), with incremental costs of $105 217 and an incremental cost-effectiveness ratio of $725 601 per QALY. To reduce the cost to $59 039 per unadjusted life-year (median household income) total drug costs must be reduced from $6173 to $452 per 3-week chemotherapy cycle.

Meaning  High US drug prices represent the best target for improving the cost-effectiveness of capecitabine and bevacizumab maintenance therapy for metastatic colorectal cancer, which is not currently cost-effective.

Abstract

Importance  Unregulated drug prices increase cancer therapy costs. After induction chemotherapy, patients with metastatic colon cancer can receive maintenance capecitabine and bevacizumab therapy based on improved progression-free survival, but whether this treatment’s cost justifies its benefits has not been evaluated in the United States.

Objective  This study sought to determine the influence of capecitabine and bevacizumab drug prices on cost-effectiveness from a Medicare payer’s perspective.

Design, Setting, and Participants  The incremental cost-effectiveness of capecitabine and bevacizumab maintenance therapy was determined with a Markov model using a quality-of-life penalty based on outcomes data from the CAIRO phase 3 randomized clinical trial (RCT), which included 558 adults in the Netherlands with unresectable metastatic colorectal cancer who had stable disease or better following induction chemotherapy. The outcomes were modeled using Markov chains to account for patients who had treatment complications or cancer progression. Transition probabilities between patient states were determined, and each state’s costs were determined using US Medicare data on payments for capecitabine and bevacizumab treatment. Deterministic and probabilistic sensitivity analyses identified factors affecting cost-effectiveness.

Main Outcomes and Measures  Life-years gained were adjusted using CAIRO3 RCT quality-of-life data to determine quality-adjusted life-years (QALYs). The primary end point was the incremental cost-effectiveness ratio, representing incremental costs per QALY gained using a capecitabine and bevacizumab maintenance regimen compared with observation alone.

Results  Markov model estimated survival and complication outcomes closely matched those reported in the CAIRO3 RCT, which included 558 adults (n = 197 women, n = 361 men; median age, 64 and 63 years for patients in the observation and maintenance therapy groups, respectively) in the Netherlands with unresectable metastatic colorectal cancer who had stable disease or better following induction chemotherapy. Incremental costs for a 3-week maintenance chemotherapy cycle were $6601 per patient. After 29 model iterations corresponding to 60 months of follow-up, mean per-patient costs were $105 239 for maintenance therapy and $21.10 for observation. Mean QALYs accrued were 1.34 for maintenance therapy and 1.20 for observation. The incremental cost-effectiveness ratio favored maintenance treatment, at an incremental cost of $725 601 per QALY. The unadjusted ratio was $438 394 per life-year. Sensitivity analyses revealed that cost-effectiveness varied with changes in drug costs. To achieve an incremental cost-effectiveness ratio of less than $59 039 (median US household income) per unadjusted life-year would require capecitabine and bevacizumab drug costs to be reduced from $6173 (current cost) to $452 per 3-week chemotherapy cycle.

Conclusions and Relevance  Antineoplastic therapy is expensive for payers and society. The price of capecitabine and bevacizumab maintenance therapy would need to be reduced by 93% to make it cost-effective, a finding useful for policy decision making and payment negotiations.

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