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Markov model

Abemaciclib, 100 mg: $99.9704 per tablet

Abemaciclib, 150 mg: $98.4714 per tablet

Abemaciclib, 200 mg: $99.9704 per tablet

ABE + exemestane: $5,552

ABE + letrozole: $5,553

ABE + tamoxifen: $5,524 to $5,534

• The sponsor used a “fixed payoff” approach that could not be fully validated by CADTH. Patients with metastatic recurrence after ABE-ET or ET were assigned a fixed number of LYs calculated using the results of pharmacoeconomic models that were not provided to CADTH as part of the current review
• The sponsor’s base case predicts a survival advantage with ABE-ET compared with ET (incremental gain: 3.60 LYs) over a 49-year horizon; however, no difference in survival was observed in the monarchE trial. Clinical experts consulted by CADTH indicated that it is highly uncertain whether delayed disease progression will translate to gains in OS. Given the sponsor’s “fixed payoff” approach, CADTH was unable to validate the survival benefit predicted for patients in the metastatic health state, introducing additional uncertainty into the sponsor’s base case.
• The long-term impact of ABE-ET on IDFS is highly uncertain. In the sponsor’s analysis, 97% of the total incremental QALYs predicted are accrued in the invasive disease-free health state, and all incremental QALYs were accrued through extrapolation. The extrapolation curve chosen by the sponsor for IDFS resulted in the incremental effectiveness of ABE-ET vs. ET increasing after patients discontinued ABE, which clinical experts considered highly uncertain.
• The sponsor assumed that the effectiveness of ABE-ET would begin to wane after 8 years (i.e., 6 years after the ABE stopping rule was imposed) and that waning would continue for a period of 19 years. The sponsor supported the assumptions using evidence from a separate class of drug with a different mechanism of action. Clinical experts consulted by CADTH considered this assumption to be implausible.
• The sponsor assumed that patients with metastatic recurrence after adjuvant ABE-ET would not receive subsequent treatment with a CDK4/6 inhibitor. Clinical experts consulted by CADTH indicated that a proportion of patients with ET-sensitive disease (recurrence at least 6 months after adjuvant ABE-ET treatment) would receive a CDK4/6 inhibitor as part of standard of care for metastatic recurrence. The assumption that no patients receive CDK4/6 inhibitors after ABE-ET likely underestimates the cost of treating metastatic recurrence and biases the ICER in favour of ABE-ET.

• Given the modelling approach adopted by the sponsor, the cost-effectiveness of ABE-ET is highly uncertain. CADTH undertook reanalyses that adopted an alternative extrapolation assumption for IDFS, which used alternative assumptions about treatment effectiveness waning. CADTH was unable to fully validate the submitted model owing to the use of a “fixed payoff” approach that relied on external models not provided to CADTH. CADTH’s base case estimate of cost-effectiveness therefore remains highly uncertain.
• Based on CADTH reanalyses, ABE-ET remained more costly and more effective than ET alone: ICER = $78,438 per QALY (incremental costs = $81,924; incremental QALYs = 1.04).
• A price reduction of at least 24% for ABE would be required for ABE-ET to be considered optimal at a WTP threshold of $50,000 per QALY compared to ET alone.
• This estimate is subject to the high degree of uncertainty due to the limitations described — most notably the “fixed payoff” approach — and further price reduction may be warranted. CADTH notes that all the predicted benefit with ABE-ET is accrued in the extrapolation period; it is uncertain whether this benefit will be realized in practice.