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. 2021 Mar 18;11(1):6306.
doi: 10.1038/s41598-021-85696-3.

Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands

Christine M Cramer-van der Welle  1 , Marjon V Verschueren  2 , Merel Tonn  2 , Bas J M Peters  2 , Franz M N H Schramel  3 , Olaf H Klungel  4 , Harry J M Groen  5 , Ewoudt M W van de Garde  2   4 ; Santeon NSCLC Study Group
Collaborators, Affiliations

Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands

Christine M Cramer-van der Welle et al. Sci Rep. .

Abstract

This study aims to assess how clinical outcomes of immunotherapy in real-world (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy-effectiveness (EE) gap. All patients diagnosed with stage IV non-small cell lung cancer (NSCLC) in 2015-2018 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. Progression-free survival (PFS) and overall survival (OS) from first-line (1L) pembrolizumab and second-line (2L) nivolumab were compared with clinical trial data by calculating hazard ratios (HRs). From 1950 diagnosed patients, 1005 (52%) started with any 1L treatment, of which 83 received pembrolizumab. Nivolumab was started as 2L treatment in 141 patients. For both settings, PFS times were comparable between real-world and trials (HR 1.08 (95% CI 0.75-1.55), and HR 0.91 (95% CI 0.74-1.14), respectively). OS was significantly shorter in real-world for 1L pembrolizumab (HR 1.55; 95% CI 1.07-2.25). Receiving subsequent lines of treatment was less frequent in real-world compared to trials. There is no EE gap for PFS from immunotherapy in patients with stage IV NSCLC. However, there is a gap in OS for 1L pembrolizumab. Fewer patients proceeding to a subsequent line of treatment in real-world could partly explain this.

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Conflict of interest statement

EvdG reports research grants from the Dutch Cancer Society during the conduct of the study, and from AbbVie NL outside the submitted work. HG reports a grant from Boehringer-Ingelheim and other from BMS, Roche, Novartis, Merck and Pfizer, outside the submitted work. All remaining authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Treatment patterns of patients diagnosed with stage IV NSCLC between 2015 and 2018 in six Dutch hospitals. BSC, best supportive care; TKI, Tyrosine Kinase Inhibitors. *1L immunotherapy: pembrolizumab: n = 83 (90%), nivolumab: n = 3 (3%), other n = 6 (7%). **2L immunotherapy: nivolumab: n = 164 (82%, of which n = 141 with non-squamous histology), pembrolizumab: n = 20 (10%), atezolizumab: n = 13 (6.5%), other: n = 3 (1.5%).
Figure 2
Figure 2
Kaplan–Meier curves of PFS and OS in patients receiving 1L pembrolizumab in real-world and clinical trial.
Figure 3
Figure 3
Kaplan–Meier curves of PFS and OS in patients receiving 2L nivolumab in real-world and clinical trial.
See this image and copyright information in PMC

References

    1. Herzberg B, Campo MJ, Gainor JF. Immune checkpoint inhibitors in non-small cell lung cancer. Oncologist. 2017;22:81–88. doi: 10.1634/theoncologist.2016-0189. - DOI - PMC - PubMed
    1. Borghaei H, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N. Engl. J. Med. 2015;373:1627–1639. doi: 10.1056/NEJMoa1507643. - DOI - PMC - PubMed
    1. Brahmer J, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N. Engl. J. Med. 2015;373:123–135. doi: 10.1056/NEJMoa1504627. - DOI - PMC - PubMed
    1. Herbst RS, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–1550. doi: 10.1016/S0140-6736(15)01281-7. - DOI - PubMed
    1. Reck M, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N. Engl. J. Med. 2016;375:1823–1833. doi: 10.1056/NEJMoa1606774. - DOI - PubMed

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