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Maintenance Pemetrexed/Pembrolizumab Versus Pembrolizumab in Non-Small Cell Lung Cancer: A Propensity Score-Weighted
Garth W Strohbehn1,2,3,4,5,6,7, Molly C Tokaz8,9, Daniel Sanghoon Shin10,11
1Veterans Affairs Center for Clinical Management Research, Ann Arbor, MI.
JCO Oncology Practice
|June 18, 2026
Summary
Adding pemetrexed to pembrolizumab maintenance therapy for non-small cell lung cancer (NSCLC) did not improve survival but increased toxicity. Re-evaluating chemotherapy components could enhance cancer care safety and cost-effectiveness.
Area of Science:
- Oncology
- Pharmacoeconomics
- Clinical Trial Analysis
Background:
- Pemetrexed is a standard maintenance therapy in combination with pembrolizumab for advanced non-small cell lung cancer (NSCLC).
- The independent contribution of pemetrexed to the survival benefit of this combination therapy is not well-established.
- Real-world data is needed to assess the effectiveness and safety of pemetrexed in contemporary NSCLC treatment regimens.
Purpose of the Study:
- To compare the real-world effectiveness and safety of maintenance pemetrexed/pembrolizumab versus pembrolizumab alone in advanced NSCLC.
- To estimate the financial impact of maintenance pemetrexed on US government payers.
- To evaluate the role of pemetrexed in the context of modern immunotherapy for NSCLC.
Main Methods:
- A propensity-weighted analysis of US Veterans Affairs data was conducted.
- Patients receiving four cycles of induction chemotherapy followed by maintenance pemetrexed/pembrolizumab or pembrolizumab alone were identified.
- Overall survival (OS) and treatment-related toxicities were primary effectiveness outcomes, while estimated government payer spending was the primary financial outcome.
Main Results:
- Maintenance pemetrexed/pembrolizumab was not associated with improved overall survival compared to pembrolizumab alone (aHR 1.06; P = .62).
- Pemetrexed use was linked to significantly higher risks of acute kidney injury (aHR 3.35), neutropenia (aHR 2.86), and anemia (aHR 1.65).
- Estimated government payer spending on maintenance pemetrexed from 2017-2022 was $1.588 billion.
Conclusions:
- Adding pemetrexed to maintenance pembrolizumab in NSCLC offers no survival advantage and increases toxicity.
- The findings suggest a need to reassess the necessity of pemetrexed in maintenance regimens to improve patient safety and healthcare costs.
- Further prospective studies are warranted to determine the incremental benefit of pemetrexed in the current immunotherapy era for NSCLC.
