Advertisement

Association Between Survival and Very High Versus High PD-L1 Expression in Patients Receiving Pembrolizumab as First-line Treatment for Advanced Non-Small Cell Lung Cancer

  • 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
    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
    Search for articles by this author
  • Melina E. Marmarelis
    Affiliations
    Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA
    Search for articles by this author
  • Ronac Mamtani
    Affiliations
    Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA
    Search for articles by this author
  • Sean Hennessy
    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
    Search for articles by this author

      Abstract

      Background

      A prior study found that, among advanced non-small cell lung cancer (aNSCLC) patients with PD-L1 expression 50% to 100% receiving immunotherapy as monotherapy, PD-L1 expression ≥ 90% was associated with longer survival. We sought to replicate this finding using real-world data from community oncology practices across the US.

      Methods

      Retrospective cohort study of aNSCLC patients who initiated pembrolizumab monotherapy for first line and had a PD-L1 expression ≥ 50% using a nationwide, deidentified longitudinal electronic health record–derived real-world database. The exposure of interest was very high PD-L1 expression, which was defined as ≥ 90%, compared to high PD-L1 expression, defined as 50% to 89%. The primary outcome was overall survival, measured from initiation of pembrolizumab to date of death, with censoring at last healthcare encounter. Multiple imputation was used to impute missing covariates. Propensity score-based inverse probability weighting (IPW) was used to address confounding in Kaplan-Meier curves and Cox proportional hazard regression models.

      Results

      The cohort included 1952 aNSCLC patients receiving first-line pembrolizumab monotherapy. Half of cohort members were female, median age was 73 years (interquartile range, 65-80), 71% had non-squamous histology, 94% had a history of smoking, and 46% had very high PD-L1 expression. Median overall survival in the propensity score-weighted sample was 15.84 months for very high PD-L1 expression and 12.72 months for high PD-L1 expression. Having a very high PD-L1 expression was associated with lower hazard of mortality (IPW hazard ratio 0.79, 95% CI 0.69-0.91).

      Conclusions

      In this large national US cohort, patients with very high PD-L1 expression (≥ 90%) aNSCLC receiving first-line pembrolizumab experienced better median survival than those with high PD-L1 expression (50% to 89%).

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Lung Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Reck M
        • Rodriguez-Abreu D
        • Robinson A.G.
        • et al.
        Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater.
        J Clin Oncol. 2019; 37: 537-546
        • Haslam A
        • Prasad V.
        Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs.
        JAMA netw open. 2019; 2e192535
        • Sezer A
        • Kilickap S
        • Gümüş M
        • et al.
        Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial.
        Lancet. 2021; 397: 592-604
        • Herbst RS
        • Giaccone G
        • de Marinis F
        • et al.
        Atezolizumab for first-line treatment of PD-l1-selected patients with NSCLC.
        N engl J med. 2020; 383: 1328-1339
        • Garon EB
        • Rizvi NA
        • Hui R
        • et al.
        Pembrolizumab for the treatment of non–small-cell lung cancer.
        New Engl J Med. 2015; 372: 2018-2028
        • Holmes M
        • Mahar A
        • Lum T
        • Kao S
        • Cooper WA.
        Real-world programmed death-ligand 1 prevalence rates in non-small cell lung cancer: correlation with clinicopathological features and tumour mutation status.
        J Clin Pathol. 2021; 74: 123-128
        • Aggarwal C
        • Abreu DR
        • Felip E
        • et al.
        Prevalence of PD-L1 expression in patients with non-small cell lung cancer screened for enrollment in KEYNOTE-001,-010, and-024.
        Ann Oncol. 2016; 27: vi363
        • Aguilar EJ
        • Ricciuti B
        • Gainor JF
        • et al.
        Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.
        Ann Oncol. 2019; 30: 1653-1659
        • Von Elm E
        • Altman DG
        • Egger M
        • et al.
        The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies.
        Int J surg. 2014; 12: 1495-1499
        • Ma X
        • Long L
        • Moon S
        • Adamson BJ
        • Baxi SS.
        Comparison of population characteristics in real-world clinical oncology databases in the US: Flatiron Health, SEER, and NPCR.
        Medrxiv, 2020
        • Abernethy AP
        • Gippetti J
        • Parulkar R
        • Revol C.
        Use of electronic health record data for quality reporting.
        J oncol pract. 2017; 13: 530-534
        • Singal G
        • Miller PG
        • Agarwala V
        • et al.
        Association of patient characteristics and tumor genomics with clinical outcomes among patients with non–small cell lung cancer using a clinicogenomic database.
        JAMA. 2019; 321: 1391-1399
        • Reck M
        • Rodríguez-Abreu D
        • Robinson AG
        • et al.
        Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer.
        N engl J med. 2016; 375: 1823-1833
        • Gainor JF
        • Shaw AT
        • Sequist LV
        • et al.
        EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non–small cell lung cancer: a retrospective analysis.
        Clin cancer res. 2016; 22: 4585-4593
        • Lantuejoul S
        • Sound-Tsao M
        • Cooper WA
        • et al.
        PD-L1 testing for lung cancer in 2019: perspective from the IASLC Pathology Committee.
        J Thorac Oncol. 2020; 15: 499-519
        • Rimm DL
        • Han G
        • Taube JM
        • et al.
        A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non–small cell lung cancer.
        JAMA oncol. 2017; 3: 1051-1058
        • Hirsch FR
        • McElhinny A
        • Stanforth D
        • et al.
        PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project.
        J Thorac Oncol. 2017; 12: 208-222
        • Zhang Q
        • Gossai A
        • Monroe S
        • Nussbaum NC
        • Parrinello CM.
        Validation analysis of a composite real-world mortality endpoint for US cancer patients.
        AACR, 2020
        • Zhang Z
        • Kim HJ
        • Lonjon G
        • Zhu Y.
        Balance diagnostics after propensity score matching.
        Ann transl med. 2019; 7: 16
        • Sterne JA
        • White IR
        • Carlin JB
        • et al.
        Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls.
        BMJ. 2009; 29: 338:b239
        • Rubin DB.
        Multiple imputation for nonresponse in surveys.
        John Wiley & Sons, 2004
        • Marshall A.
        • Altman D.G.
        • Holder R.L.
        • Royston P.
        Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines.
        BMC Med Res Methodol. 2009; 9: 57
        • Schoenfeld D.
        Partial residuals for the proportional hazards regression model.
        Biometrika. 1982; 69: 239-241
        • Edahiro R
        • Kanazu M
        • Kurebe H
        • et al.
        Clinical outcomes in non-small cell lung cancer patients with an ultra-high expression of programmed death ligand-1 treated using pembrolizumab as a first-line therapy: a retrospective multicenter cohort study in Japan.
        PLoS One. 2019; 14e0220570
        • Alessi JV
        • Ricciuti B
        • Jiménez-Aguilar E
        • et al.
        Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥ 50%) non–small cell lung cancer and a poor performance status.
        J immunother cancer. 2020; 8: e001007
        • Doroshow DB
        • Wei W
        • Gupta S
        • et al.
        Programmed death-ligand 1 tumor proportion score and overall survival from first-line Pembrolizumab in patients with nonsquamous versus squamous NSCLC.
        J Thorac Oncol. 2021; 16: 2139-2143
        • Kernan WN
        • Viscoli CM
        • Makuch RW
        • Brass LM
        • Horwitz RI.
        Stratified randomization for clinical trials.
        J clinic epidemiol. 1999; 52: 19-26