Presentation (CTI)

OBJECTIVES: The PHERGain trial evaluated a PET-guided, pathological complete response (pCR)-adapted, chemotherapy-free strategy based on dual HER2 blockade in patients with HER2-positive early breast cancer (EBC). Building on this approach, we assessed the cost-effectiveness of a PET-guided de-escalation strategy versus standard neoadjuvant chemotherapy (TCHP).
METHODS: A hybrid decision tree/Markov model was developed to estimate the economic outcomes of a PET-guided de-escalation strategy versus TCHP in patients with HER2-positive EBC from a US healthcare sector perspective over a lifetime horizon. The decision tree captured initial treatment pathways and responses based on PHERGain (including PET response and pCR), followed by a Markov model with six health states: invasive disease-free survival (iDFS), nonmetastatic recurrence, remission, first-line and second-line metastatic breast cancer, and death. Transition probabilities were derived from PHERGain and supplemented with published evidence. Costs and utilities were obtained from previous literature. Outcomes were expressed as incremental cost-effectiveness ratios (ICERs) and evaluated against a willingness-to-pay threshold of $150,000 per QALY. Probabilistic sensitivity analysis (PSA) was conducted to characterize parameter uncertainty.
RESULTS: The PET-guided strategy was associated with higher costs and lower QALYs than TCHP and was therefore dominated, with an incremental cost of $254,454 and a QALY loss of 0.27. PSA showed consistent results, with 96% of simulations favoring TCHP and a low probability of cost-effectiveness across willingness-to-pay thresholds. Scenario analyses yielded similar findings.
CONCLUSIONS: PET-guided de-escalation is unlikely to be cost-effective compared with TCHP, despite potential quality-of-life benefits, and is not supported for routine adoption under current evidence and cost structures from a policy perspective.