Analysis of KEYNOTE-A18 Trial Finds Keytruda is Not Cost-Effective at Current Prices
Analysis shows the addition of Keytruda (pembrolizumab) to standard chemoradiotherapy for newly diagnosed, locally advanced cervical cancer is not cost-effective at its current price.
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A cost-effectiveness analysis of results from the Phase III ENGOT-cx11/GOG-3407/KEYNOTE-A18 clinical trial (NCT04221945) found that the addition of concurrent and adjuvant Keytruda (pembrolizumab) to standard chemoradiotherapy in patients with newly diagnosed, locally advanced cervical cancer was not cost-effective at current prices for the drug. These findings, published by JAMA Network Open, indicate that lowering the price of Keytruda by 45.6% or using a shorter treatment duration could meet the threshold for cost-effectiveness.1,2
“In cervical cancer specifically, the addition of pembrolizumab to chemotherapy was not found to be cost-effective for the treatment of persistent, recurrent, or metastatic disease in several cost-effectiveness studies, although 2 others did find this regimen to be cost-effective,” the study authors wrote. “However, the cost-effectiveness of pembrolizumab may differ in the frontline, definitive treatment setting. Health care economic concerns are distinctly relevant for cervical cancer not only because of its overall incidence, but also because of the well-established association between cervical cancer outcomes and patient socioeconomic factors.”1
Keytruda is an anti-PD-1 therapy that improves the immune system's ability to detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which leads to the activation of T lymphocytes that could affect the tumor and healthy cells.
To date, more than 1600 trials are evaluating Keytruda across a range of cancer types and treatment settings. Keytruda also has approved indications in melanoma; non-small cell lung cancer; head and neck squamous cell cancer; classical Hodgkin lymphoma; primary mediastinal large B-cell lymphoma; urothelial carcinoma; gastric cancer; microsatellite instability-high or mismatch repair deficient cancer; microsatellite instability-high or mismatch repair deficient colorectal cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel cell carcinoma; renal cell carcinoma; endometrial carcinoma; tumor mutational burden-high cancer; cutaneous squamous cell carcinoma; and triple-negative breast cancer.3
Trial Design
The randomized, double-blind, KEYNOTE-A18 trial evaluated Keytruda with cisplatin and EBRT followed by concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in newly diagnosed patients with stage IB2-IIB lymph node-positive locally advanced cervical cancer, and patients with stage III-IVA with and without lymph node-positive, locally advanced cervical cancer, in which patients were treated with definitive intent. In addition to the primary endpoints of progression-free survival (PFS) and overall survival (OS), secondary endpoints included complete response rate, objective response rate, and safety.
Investigators enrolled 1,060 patients with cervical cancer who were not previously treated with any definitive surgery, radiation, or systemic therapy for cervical cancer. Patients were randomly assigned at 1:1 ratio to receive either Keytruda at a dose of 200 mg intravenously (IV) every three weeks for five cycles concurrent with cisplatin at a dose of 40 mg/m2 IV weekly for five cycles and radiotherapy with EBRT followed by concurrent chemoradiotherapy, followed by Keytruda 400 mg IV every six weeks for 15 cycles; or placebo IV every three weeks for five cycles concurrent with cisplatin 40 mg/m2 IV weekly for five cycles and EBRT followed by concurrent chemoradiotherapy, followed by placebo IV every six weeks for 15 cycles.
The results show that Keytruda plus chemoradiotherapy achieved the study’s primary endpoint of OS as well as a statistically significant and clinically meaningful improvement in PFS compared with concurrent chemoradiotherapy alone.4
For the current study, investigators developed a Markov model to simulate 50-year outcomes to analyze cost-effectiveness from a payer perspective for patients administered Keytruda or placebo plus chemoradiotherapy with brachytherapy. Results such as disease progression, survival, and treatment-related adverse effects were gathered from KEYNOTE-A18 data. They calculated costs and health utilities from published literature and conducted probabilistic sensitivity analyses used to evaluate model uncertainty.
They found that use of Keytruda increased costs by $257,000 and effectiveness by 1.40 quality-adjusted life years (QALYs), yielding an incremental cost-effectiveness ratio of $183,400 per QALY. Use of Keytruda was deemed cost-effective if the monthly price dropped from $16,990 to $9,190 or the maximum treatment duration of 24 months dropped to 10 months. A probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100,000 per QALY, use of Keytruda was cost-effective 37.3% of the time.
“These expensive treatments may ultimately be detrimental to these disadvantaged groups and exacerbate existing disparities as the result of financial toxicity or inability to afford the most clinically beneficial drugs. Although the US Food and Drug Administration (FDA) recently approved pembrolizumab with chemoradiotherapy and brachytherapy for the treatment of FIGO 2014 stage III-IVA cervical cancer, FDA approval of a drug does not mandate insurance coverage,” the study authors concluded. “Even with insurance coverage, a large proportion of patients with cervical cancer are underinsured or uninsured and therefore may still be subject to high out-of-pocket costs. If this pembrolizumab-based regimen assessed in our study is to be implemented into the standard of care for locally advanced cervical cancer, care must be taken so as to not financially harm an already at-risk population.”1
References
1. 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. doi:10.1001/jamanetworkopen.2025.0033
2. Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047). ClinicalTrials.gov. January 22, 2025. Accessed March 5, 2025. https://clinicaltrials.gov/study/NCT04221945
3. Merck Announces Phase 3 KEYNOTE-522 Trial Met its Overall Survival (OS) Endpoint in Patients With High-Risk Early-Stage Triple Negative Breast Cancer (TNBC). News release. Merck. May 28, 2024. Accessed March 5, 2025. https://www.merck.com/news/merck-announces-phase-3-keynote-522-trial-met-its-overall-survival-os-endpoint-in-patients-with-high-risk-early-stage-triple-negative-breast-cancer-tnbc/
4. Merck’s KEYTRUDA® (pembrolizumab) Plus Chemoradiotherapy (CRT) Significantly Improved Overall Survival (OS) Versus CRT Alone in Patients With Newly Diagnosed High-Risk Locally Advanced Cervical Cancer. Merck. News release. March 15, 2024. Accessed March 5, 2025. https://www.merck.com/news/mercks-keytruda-pembrolizumab-plus-chemoradiotherapy-crt-significantly-improved-overall-survival-os-versus-crt-alone-in-patients-with-newly-diagnosed-high-risk-locally-advanced-ce/
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