Evidence map›Paper›PMID 41193345›Full record

ArticleClinical lung cancer2026

Real-World Effectiveness of Second-Line Therapies in Advanced Non-Small Cell Lung Cancer: Insights From Propensity-Weighted Comparative Analyses of Longitudinal EHR Data.

Gary C N Hettinger, Qi Long, Ravi B Parikh

Abstract readComparative Study
In one paragraph

Article in Clinical lung cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Gary C N HettingerDepartment of Population Health, New York University Grossman School of Medicine, New York, NY; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Electronic address: gary.hettinger@nyulangone.org.
Qi LongDepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Ravi B ParikhDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA.

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Robust privacy preserving distributed analysis platform for cancer research: addressing data bias and disparitiesU01CA274576 · NCI · UNIVERSITY OF PENNSYLVANIA · PI JIANG, XIAOQIAN, LONG, QI · 2023 to 2025
$1.2M
NCI NIH HHS P30 CA016520NCI NIH HHS U01 CA274576
6 · The paper itself

Abstract

backgroundWhile substantial research has focused on first-line (1L) therapies for advanced-stage non-small cell lung cancer (aNSCLC), less is known about the effectiveness of second-line (2L) treatments following disease progression on 1L. The poor prognosis after 1L progression, limited guidance for 2L treatment, and constraints of clinical trials in addressing these questions underscore the need for real-world comparative effectiveness research.

methodsWe conducted a retrospective analysis to compare real-world overall survival (rwOS) associated with 2L treatments among patients with disease progression during 1L. Eligible patients were selected from Flatiron Health's nationwide electronic health record (EHR)-derived de-identified database. 1L and 2L treatments were categorized as chemotherapy-only (Chemo-alone), combination chemo- and immunotherapy (Chemo + Immuno), immunotherapy-only (IO-alone), targeted-alone therapy, or targeted-plus therapy. We used inverse probability of treatment weighting to adjust for extensive static and longitudinal patient-level confounding and compared rwOS using Kaplan-Meier curves and restricted mean survival time (RMST).

resultsAmong patients previously treated with 1L Targeted therapy, those receiving 2L Targeted-alone therapy had longer life expectancies than those receiving a nontargeted (ΔRMST-36 + 2.61 months) or Targeted-plus regimen (ΔRMST-36 + 3.11 months). For patients progressing on 1L Chemo + Immuno, 2L Chemo + Immuno outperformed Chemo-alone (ΔRMST-36 + 2.98 months). Among patients progressing ≥1 year after initiating 1L IO-alone, 2L Chemo + Immuno again showed better life expectancy than Chemo-alone (ΔRMST-36 + 5.70 months).

conclusionsLongitudinal real-world data can enhance assessment of 2L therapy effectiveness. After confounder adjustment, we found clinically meaningful survival differences by 2L choice. These findings underscore the importance of 2L treatment selection and the need for prospective validation.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungElectronic Health RecordsImmunotherapyLung NeoplasmsAgedAged, 80 and overComparative Effectiveness ResearchFemaleFollow-Up StudiesHumansLongitudinal StudiesMaleMiddle AgedPrognosisPropensity ScoreBiomarkerCausal inferenceChemotherapyImmunotherapyTargeted therapy

Identifiers

PMID41193345
PMCPMC13092172

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.