WCLC 2025 - Posters & ePosters-P2.10.01 Maintenance Pemetrexed/Pembrolizumab vs Maintenance Pembrolizumab Alone in Advanced Non-Squamous Non-Small Cell Lung Cancer

P2.10.01 Maintenance Pemetrexed/Pembrolizumab vs Maintenance Pembrolizumab Alone in Advanced Non-Squamous Non-Small Cell Lung Cancer

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This study evaluates whether adding maintenance pemetrexed to pembrolizumab treatment offers survival benefits in patients with advanced/metastatic non-squamous non-small cell lung cancer (NSCLC). Current U.S. federal regulations require that combination cancer therapies demonstrate the “contribution of component” (CoC) to justify their use, yet this is rarely enforced. In the KEYNOTE-189 trial, all patients received maintenance pemetrexed, leaving its necessity unproven when combined with pembrolizumab.<br /><br />Using data from 622 U.S. veterans treated between 2017 and 2024, the study compares outcomes of maintenance pembrolizumab alone versus pembrolizumab plus pemetrexed after induction therapy. Effectiveness measures included overall survival (OS) and time-to-next treatment (TTNT), while safety was assessed through all-cause hospitalization and grade ≥3 kidney and hematologic toxicities. Propensity-score adjusted Cox models and Kaplan-Meier survival curves were used for analysis.<br /><br />Key findings indicate no clear survival benefit from adding pemetrexed to pembrolizumab maintenance. There was a trend toward improved survival in patients with PD-L1 expression ≥1%, but this was not definitive. Conversely, maintenance pemetrexed was associated with added risks, including increased toxicity and higher costs. Notably, the dosing schedule of pemetrexed complicates pembrolizumab administration, potentially reducing patient convenience and increasing drug spending, which exceeded $1.5 billion by U.S. government payers from 2017 to 2022.<br /><br />The authors suggest that maintenance pemetrexed may represent an unnecessary inefficiency in treatment, contributing to clinical toxicity, time burden, and financial costs without clear benefit. They argue that reassessing the role of legacy therapies like maintenance pemetrexed in the immunotherapy era could lead to improved care and cost savings. A VA-based randomized controlled trial is planned to test withdrawal of maintenance pemetrexed formally. The study highlights the importance of strict regulatory enforcement of CoC for combination therapies in oncology to optimize treatment value.

Asset Subtitle

Garth Strohbehn

Meta Tag

Speaker Garth Strohbehn

Topic Metastatic Non-small Cell Lung Cancer – Cytotoxic Therapy

Keywords

pemetrexed

pembrolizumab

non-small cell lung cancer

maintenance therapy

KEYNOTE-189 trial

overall survival

PD-L1 expression

toxicity

combination cancer therapy

contribution of component