Related Experiment Video
Updated: Jun 20, 2026
Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
Published on: February 7, 2021
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.
Purpose:
Pemetrexed remains part of guideline-recommended maintenance pemetrexed/pembrolizumab in advanced/metastatic non-oncogene-driven nonsquamous non-small cell lung cancer (NSCLC). Whether pemetrexed contributes to the combination's survival benefit is unknown. In this propensity-weighted analysis of US Veterans Affairs data, we compared real-world effectiveness and safety of maintenance pemetrexed/pembrolizumab versus maintenance pembrolizumab alone and estimated US government payer spending on maintenance pemetrexed.
Methods:
We identified Veterans who received four cycles of carboplatin/cisplatin, pemetrexed, and pembrolizumab followed by at least one dose of maintenance pemetrexed/pembrolizumab or pembrolizumab. A propensity-weighted Cox model was used to adjust for baseline between-group differences using inverse probability of treatment weights. The primary effectiveness outcome was overall survival (OS; time from first maintenance dose to death). The primary financial outcome was the estimated spending on maintenance pemetrexed across VA, Medicare Part B, and Medicaid (2017-2022).
Results:
The real-world outcomes cohort included 622 patients (473 pemetrexed/pembrolizumab; 149 pembrolizumab alone). After propensity weighting, pemetrexed was not associated with improved OS (adjusted hazard ratio [aHR] pemetrexed/pembrolizumab v pembrolizumab, 1.06 [95% CI, 0.83 to 1.36, P = .62]) but was associated with higher toxicity risk (grade ≥3 acute kidney injury [aHR 3.35, 95% CI, 1.08 to 10.41, P = .04]; neutropenia [aHR 2.86, 95% CI, 1.44 to 3.05; P = .004]; anemia [aHR 1.65, 95% CI, 1.11 to 2.47, P = .014]). Findings were robust to sensitivity analysis in which patients who crossed over from pembrolizumab to pemetrexed/pembrolizumab were excluded. Estimated government payer spending on maintenance pemetrexed from 2017 to 2022 totaled $1.588 billion (2024 USD).
Conclusion:
Adding pemetrexed to maintenance pembrolizumab was not associated with improved survival but was associated with increased toxicity. Reassessing legacy chemotherapy components may improve the safety and cost-effectiveness of cancer care. Prospective evaluation of maintenance pemetrexed's incremental benefit in NSCLC in the immunotherapy era is needed.
