Cost-effectiveness Analysis of Ado-trastuzumab Emtansine (T-DM1) for the Adjuvant Treatment of Patients With Residual Invasive HER2+ Early Breast Cancer in the United States

Abstract

Objective: Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States. Materials and Methods:A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature.Results: T-DM1 dominated trastuzumab, yielding lower lifetime costs (−$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results. Conclusion:Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes.

Residual Disease Burden After Neoadjuvant Therapy Among US Patients With High-Risk HER2-positive Early-Stage Breast Cancer: A Population Effectiveness Model

“…Similarly, Sussell et al found that treatment with T-DM1 was cost-saving and improved outcomes compared with trastuzumab. 27 In summary, to our knowledge, no previous studies have evaluated the residual burden of disease in a patient population similar to that of the KATHERINE trial, multiple studies have suggested that novel treatments to reduce the residual burden of recurrence in persons with HER2-positive ESBC could be cost-effective.…”

Whether and How Disutilities of Adverse Events were Used in the Economic Evaluation of Drug Therapy for Cancer Treatment

“…Third, the AEs seen had little impact on quality of life because of their low incidence or mild severity (32%, 11/34), as in the study by Mulder et al [ 43 ] Fourth, no disutilities data were available (6%, 2/34). The study of Sussell et al [ 44 ] did not consider AE-related disutility for both the third and fourth reasons. Fifth, no disutility values were attributed to AEs to match other economic evaluations (6%, 2/34), as in the study by Takushima et al [ 45 ].…”

Research Trend of Publications Concerning Antibody-Drug Conjugate in Solid Cancer: A Bibliometric Study

“…Genentech Inc.’s reputation in the ADC field is ascribed to the design of T-DM1, which has been approved for advanced and early breast cancer in 2013 and 2019 by the FDA ( Boyraz et al, 2013 ; Von Minckwitz et al, 2019 ). Aside from that, they’ve studied T-DM1 as an adjuvant for breast cancer, as well as its cost-effectiveness and drug resistance in recent years ( Boyer et al, 2021 ; Mamounas et al, 2021 ; Sussell et al, 2021 ). Genentech Inc., also devotes itself to studying the mechanisms, pharmacokinetics, and structures of ADCs and to developing novel ADC agents.…”