Pembrolizumab Raises Costs Without Meeting US Cost-Effectiveness Threshold in Locally Advanced Cervical Cancer
Key Clinical Summary
- In a US payer–perspective model using KEYNOTE-A18 data, adding concurrent and adjuvant pembrolizumab to chemoradiotherapy and brachytherapy raised costs by $257 000 and gained 1.40 quality-adjusted life year (QALY), for an ICER of $183 400/QALY.
- At a $100 000/QALY willingness-to-pay threshold, the regimen was not cost-effective; probability of cost-effectiveness was 37.3% in probabilistic analysis.
- Cost-effectiveness could be achieved with a 45.6% monthly price reduction (to $9190) or by limiting total duration to 10 months.
The addition of pembrolizumab to first-line chemoradiotherapy and brachytherapy for newly diagnosed, locally advanced cervical cancer improved effectiveness but did not meet conventional US cost-effectiveness thresholds. Investigators reporting in JAMA Network Open built a payer-perspective economic model populated with outcomes from the phase III ENGOT-cx11/GOG-3407/KEYNOTE-A18 randomized trial. The analysis addresses whether survival gains from pembrolizumab justify higher drug and care costs in the US.
Study Findings
Researchers developed a Markov model simulating 50-year outcomes for patients receiving chemoradiotherapy plus brachytherapy with pembrolizumab or placebo, reflecting KEYNOTE-A18 (n = 1060; median age, 50 years). Transition probabilities for progression, survival, and grade 3–5 toxic effects were derived from trial data; costs (2024 USD) and utilities came from published literature, with 3% annual discounting.
Base-case results showed overall costs of $363 200 for pembrolizumab versus $106 200 for placebo, a $257 000 increase. Effectiveness rose from 10.50 to 11.90 QALYs (gain, 1.40 QALYs), producing an ICER of $183 400/QALY—exceeding the $100 000/QALY willingness-to-pay threshold. From a societal perspective, the ICER was $199 100/QALY.
One-way sensitivity analyses indicated moderate sensitivity to pembrolizumab price and duration. Cost-effectiveness could be achieved if the monthly cost fell from $16 990 to $9190 (–45.6%) or if the maximum duration decreased from 24 to 10 months. Scenario analyses suggested ICERs of $50 000/QALY if given only concurrently (5 triweekly cycles; ~4 months) and a cost-effective adjuvant-only strategy up to 11 months. The model was otherwise insensitive to assumptions about toxic effects, progression-free survival, and overall survival. Probabilistic sensitivity analysis found a 37.3% chance of cost-effectiveness at $100 000/QALY; this rose to 53.9% at $150 000/QALY.
Clinical Implications
For US oncology practices and payers, the findings underscore a misalignment between clinical benefit and current pricing/duration of pembrolizumab in the definitive treatment of locally advanced cervical cancer. While KEYNOTE-A18 demonstrated survival improvement, the modeled ICER exceeds commonly cited US thresholds, suggesting limited value at present prices under typical payer benchmarks.
The analysis highlights two actionable levers: price and duration. Contracting or outcomes-based agreements that effectively lower net price, or protocol modifications that cap treatment duration, could bring the regimen within accepted cost-effectiveness ranges—pending evidence that shorter courses preserve clinical benefit. Given persistent disparities in cervical cancer outcomes and risks of financial toxicity, formulary decisions and pathway updates should weigh these economic outcomes alongside efficacy and safety. Health-system leaders may also consider prioritizing financial counseling and access programs for underinsured patients.
Conclusion
Based on a US payer–perspective economic evaluation using KEYNOTE-A18 outcomes, adding pembrolizumab to chemoradiotherapy and brachytherapy for newly diagnosed, locally advanced cervical cancer is not cost-effective at current pricing and duration. Price reductions or shorter courses may improve value, contingent on maintaining clinical efficacy.
Reference
Courtney PT, Venkat PS, Shih YT, et al. Cost-effectiveness of pembrolizumab with chemoradiotherapy for locally advanced cervical cancer. JAMA Netw Open. 2025;8(3):e250033. Published 2025 Mar 3. doi:10.1001/jamanetworkopen.2025.0033
