Economic evaluation of rituximab in addition to standard of care chemotherapy for adult patients with acute lymphoblastic leukemia.

AIMS: Acute lymphoblastic leukemia (ALL) is an aggressive form of leukemia with a poor prognosis in adult patients. The addition of the monoclonal antibody rituximab to standard chemotherapy has been shown to improve survival in adults with ALL. However, it is unknown whether the addition of rituximab is cost-effective. The objective was to determine the economic impact of rituximab in addition to standard of care (SOC) chemotherapy vs SOC alone in newly-diagnosed Philadelphia chromosome-negative, CD20-positive, B-cell precursor ALL. METHODS: A decision analytic model was constructed, based upon the Canadian healthcare system. It included the following health states over a lifetime horizon (max ≈60 years): event-free survival (EFS), relapsed/resistant disease, cure, and death. SOC was either hyper-CVAD or the Dana Farber Cancer Institute (DFCI) ALL consortium. EFS, overall survival, and serious adverse event (SAE) rates were derived from a large randomized controlled trial. Costs of the model included: first-line treatment and administration, disease management, second-line and third-line treatment and administration, palliative care, and SAE-related treatments. Inputs were sourced from provincial and national public data, the literature, and cancer agency input. RESULTS: Quality-adjusted life-years (QALYs) increased by 2.20 QALYs with rituximab in addition to SOC. The resulting mean Incremental Cost-Effectiveness Ratio (ICER) was C$21,828/QALY. At a willingness-to-pay threshold of C$100,000/QALY, the probability of being cost-effective was 98%. Decision outcomes were robust to the probabilistic and deterministic sensitivity analyses, including the SOC backbone as either hyper-CVAD or DFCI. LIMITATIONS: The results of this analysis are limited by generalizability of the chemotherapy backbone to Canadian practice. CONCLUSIONS: For adults with ALL, rituximab in addition to SOC was found to be a cost-effective intervention, compared to SOC alone. The addition of rituximab is associated with increased life years and increased QALYs at a reasonable incremental cost.

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System.

BACKGROUND AND OBJECTIVES: Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers. METHODS: An Excel-based model was utilized to estimate the relevant costs. Clinical data were obtained from the EMILIA trial. Cost information was obtained from the literature, clinical experts, and standard cost sources. The analysis was conducted from the Canadian public-payer perspective and reported in 2014 Canadian dollars (CAD). RESULTS: The management of included treatment-related AEs resulted in higher estimated per-patient costs of CAD6901 for CAP + LAP versus CAD3380 for T-DM1, resulting in savings of CAD3521. CONCLUSIONS: From a Canadian perspective, this analysis demonstrated that utilizing T-DM1 for the management of HER2-positive metastatic breast cancer results in substantial savings to the public health-care system when considering the costs of treatment-related AEs, due to fewer amount of toxicities compared with CAP + LAP. Results of various sensitivity analyses investigating changes in number and costs of AEs confirmed the findings; however, the magnitude of cost savings varied. Further analyses are necessary to determine whether these cost savings would occur in other countries and health-care systems.

Economic analysis of bevacizumab, cetuximab, and panitumumab with fluoropyrimidine-based chemotherapy in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC).

OBJECTIVE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers). Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to human vascular endothelial growth factor. A sub-study confirmed its effectiveness in KRAS wild-type patients. Recent evidence has shown clinical benefit from anti-epidermal growth factor treatments cetuximab and panitumumab in these patients. The cost-effectiveness, to the Canadian healthcare system, of fluoropyrimidine-based chemotherapy (FBC) in combination with bevacizumab, cetuximab, or panitumumab was assessed for first-line treatment of KRAS wild-type mCRC patients. METHODS: A Markov model was developed and calibrated to progression-free/overall survival, using separately reported trial survival and adverse event results for each comparator. Health-state resource utilization was derived from published data and oncologist input. Utilities and unit prices were obtained from published literature and standard Canadian sources. RESULTS: Results per patient are over a lifetime horizon, to a maximum of 10 years, with 5% annual discounting. Comparators are ordered by total cost and the incremental cost-effectiveness ratio (ICER) of each is determined against the previous non-dominated therapy. Compared to FBC alone, bevacizumab + FBC has an ICER of $131,600 per QALY gained. Compared to bevacizumab + FBC, panitumumab + FBC is dominated and cetuximab + FBC has an ICER of $3.8 million per QALY. In probabilistic sensitivity analysis, bevacizumab + FBC had ∼100%, ∼100%, and 98.9% probabilities of being more cost-effective than both of the other combination treatments at thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, respectively. CONCLUSION: For first-line treatment of KRAS-WT mCRC, bevacizumab + FBC is associated with substantially lower costs as compared to panitumumab + FBC or cetuximab + FBC. Key limitations were that survival curves and adverse event rates were taken from separate clinical trials and that an indirect comparison was not included. Given these findings, bevacizumab is likely to offer the best value for money for this patient population.