Abstract
IMPORTANCE: The KEYNOTE-A18 trial demonstrated that adding concurrent and adjuvant pembrolizumab to chemoradiotherapy and brachytherapy significantly improved survival in patients with newly diagnosed, locally advanced cervical cancer. However, considering the annual global incidence of 660 000 cases of cervical cancer, including 13 820 in the US in 2024, incorporating this regimen into the standard of care could have substantial health care economic implications for both patients and the health care system. OBJECTIVE: To determine the cost-effectiveness of adding pembrolizumab to the first-line treatment of newly diagnosed, locally advanced cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation created a Markov model simulating 50-year outcomes to evaluate cost-effectiveness from the payer perspective for patients receiving either pembrolizumab or placebo in addition to chemoradiotherapy plus brachytherapy. Probabilities, including disease progression, survival, and treatment-related toxic effects, were derived from KEYNOTE-A18 clinical trial data in patients with newly diagnosed, locally advanced cervical cancer. Costs and health utilities were obtained from published literature; 1-way, 3-way, and probabilistic sensitivity analyses were used to assess model uncertainty. Data analyses were conducted from April to November 2024. EXPOSURE: Pembrolizumab. MAIN OUTCOMES AND MEASURES: Costs, measured in 2024 US dollars, and effectiveness, measured in quality-adjusted life-years (QALYs) were used to calculate an incremental cost-effectiveness ratio (ICER). A willingness-to-pay threshold of $100 000 per QALY was chosen, below which pembrolizumab would be considered cost-effective. RESULTS: KEYNOTE-A18 enrolled 1060 patients (529 in pembrolizumab group, 531 in placebo group). The median age was 50 years. Pembrolizumab increased costs by $257 000 and effectiveness by 1.40 QALYs, yielding an incremental cost-effectiveness ratio of $183 400 per QALY. The addition of pembrolizumab became cost-effective if its monthly cost was decreased from $16 990 to $9190 (a 45.6% reduction) or its maximum duration of 24 months was decreased to 10 months. The model was insensitive to assumptions about treatment-related toxic effects, progression-free survival, and overall survival. Probabilistic sensitivity analysis indicated that at a willingness-to-pay threshold of $100 000 per QALY, the addition of pembrolizumab was cost-effective 37.3% of the time. CONCLUSIONS AND RELEVANCE: In this economic evaluation of adding concurrent and adjuvant pembrolizumab to first-line treatment of newly diagnosed, locally advanced cervical cancer, this regimen was not cost-effective at current prices despite data demonstrating improved survival with this regimen.