A comprehensive cost-effectiveness analysis of the Phase III KEYNOTE-A18 trial has revealed that adding Keytruda (pembrolizumab) to standard chemoradiotherapy for newly diagnosed, locally advanced cervical cancer is not cost-effective at current pricing levels, despite showing significant clinical benefits.
The economic analysis, published in JAMA Network Open, demonstrates that the addition of Keytruda increases healthcare costs by $257,000 while improving effectiveness by 1.40 quality-adjusted life years (QALYs). This results in an incremental cost-effectiveness ratio of $183,400 per QALY, exceeding typical willingness-to-pay thresholds.
Clinical Benefits vs. Economic Reality
The KEYNOTE-A18 trial, which enrolled 1,060 previously untreated cervical cancer patients, demonstrated positive clinical outcomes. The study achieved its primary endpoint of overall survival and showed statistically significant improvement in progression-free survival when combining Keytruda with chemoradiotherapy compared to chemoradiotherapy alone.
Patients received either Keytruda (200 mg intravenously every three weeks for five cycles) or placebo, along with cisplatin and external beam radiation therapy (EBRT). The Keytruda arm continued with 400 mg doses every six weeks for 15 additional cycles.
Economic Analysis and Potential Solutions
Researchers utilized a Markov model to simulate 50-year outcomes from a payer perspective. The analysis revealed two potential paths to achieving cost-effectiveness:
- Reducing Keytruda's monthly price from $16,990 to $9,190
- Shortening the maximum treatment duration from 24 months to 10 months
At current pricing, probabilistic sensitivity analysis showed Keytruda was cost-effective only 37.3% of the time at a willingness-to-pay threshold of $100,000 per QALY.
Impact on Healthcare Disparities
The high cost of Keytruda raises significant concerns about healthcare accessibility, particularly given the well-documented relationship between cervical cancer outcomes and socioeconomic factors. While the FDA has approved Keytruda with chemoradiotherapy for FIGO 2014 stage III-IVA cervical cancer, approval does not guarantee insurance coverage.
The study authors emphasize that implementing this treatment regimen as standard care could potentially harm an already vulnerable patient population, particularly affecting underinsured or uninsured patients who may face substantial out-of-pocket costs.
Therapeutic Context
Keytruda functions as an anti-PD-1 therapy, enhancing the immune system's ability to detect and fight tumor cells by blocking the interaction between PD-1 and its ligands. The drug has received approval for multiple cancer indications, with over 1,600 ongoing trials across various cancer types and treatment settings.
The findings underscore the growing tension between therapeutic advances and healthcare economics, particularly in diseases that disproportionately affect economically disadvantaged populations. As innovative treatments continue to emerge, balancing clinical efficacy with cost-effectiveness remains a critical challenge in oncology care.
