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Original Study|Articles in Press

Chemoimmunotherapy vs. Immunotherapy for First Line Treatment of Advanced Non–small Cell Lung Cancer With a PD-L1 Expression ≥50% or ≥90%

  • Mohsin Shah
    Correspondence
    Address for correspondence: Mohsin Shah, MBBS, MSCE, Center for Real-world Effectiveness and Safety of Therapeutics (CREST), and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104.
    Affiliations
    Center for Real-world Effectiveness and Safety of Therapeutics (CREST), and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA

    Epidemiology and Drug Safety, IQVIA Real World Solutions, Wayne, PA
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  • Ronac Mamtani
    Affiliations
    Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA
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  • Author Footnotes
    # co-senior authors
    Melina E. Marmarelis
    Footnotes
    # co-senior authors
    Affiliations
    Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA
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  • Author Footnotes
    # co-senior authors
    Sean Hennessy
    Footnotes
    # co-senior authors
    Affiliations
    Center for Real-world Effectiveness and Safety of Therapeutics (CREST), and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA
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  • Author Footnotes
    # co-senior authors
Published:February 28, 2023DOI:https://doi.org/10.1016/j.cllc.2023.02.007

      Abstract

      Background

      Evidence about the comparative effectiveness of chemoimmunotherapy vs. immunotherapy alone in patients with advanced non–small cell lung cancer (aNSCLC) and high PD-L1 expression (≥50%) or very high PD-L1 expression (≥90%) is limited because of the lack of head-to-head clinical trials.

      Objective

      To compare survival in aNSCLC patients receiving first-line chemoimmunotherapy vs. immunotherapy in both the PD-L1 expression ≥50% or ≥90% subgroups, accounting for potential confounders that may influence physician decision-making.

      Methods

      This cohort study used a nationwide electronic health record derived database to identify newly diagnosed cases of aNSCLC patients with PD-L1 expression of ≥50% who initiated first-line systemic therapy between October 2016 and October 2021.
      The exposure of interest was first-line therapy with chemoimmunotherapy or immunotherapy among patients with PD-L1 expression ≥50% or ≥90%.
      Survival was assessed using Kaplan-Meier curves and Cox regression. Propensity score-based inverse probability of weighting (IPW) was used to control for confounding. Because of nonproportionality of hazards, we estimated hazard ratios over the first 6 months and after 6 months for the overall cohort, and over the first 12 months and after 12 months for a subgroup of persons with a PD-L1 expression ≥90%.

      Results

      We identified 3086 subjects who met inclusion criteria, of whom 32% received chemoimmunotherapy and 68% received immunotherapy alone. Chemoimmunotherapy was associated with no survival advantage vs. immunotherapy alone during the entire follow-up period (IPW-adjusted Hazard Ratio [aHR] 0.98, 95% CI, 0.86-1.12), but was associated with a survival benefit during the first 6 months (aHR 0.74, 95% CI, 0.61-0.90). Similarly, in the subgroup of patients with a PD-L1 expression ≥90%, chemoimmunotherapy was associated with no overall survival advantage during the entire follow-up period (aHR 0.99, 95% CI, 0.87-1.22), but was associated with a survival benefit during the first 12 months (aHR 0.74, 95% CI, 0.57-0.97).

      Conclusion

      Chemoimmunotherapy was not associated with an overall benefit over immunotherapy alone, although was associated with an early survival advantage in both the overall cohort and the subgroup of patients with a PD-L1 expression ≥90%. Future studies should focus on identifying the characteristics of higher risk patients that may benefit from the addition of chemotherapy.

      Keywords

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