Abstract
Background
Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.
Methods
We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50%.
Results
One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p < 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90%, as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis.
Conclusion
Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.
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Availability of data and materials
The datasets used during the present study are available from the corresponding author upon reasonable request.
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Acknowledgements
A special thanks to the “Consorzio Interuniversitario Nazionale per la Bio‑Oncologia” for their support in this study.
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All authors contributed to the publication according to the ICMJE guidelines for the authorship (study conception and design, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision). All authors read and approved the submitted version of the manuscript (and any substantially modified version that involves the author’s contribution to the study). Each author have agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
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Dr. Alessio Cortellini received speaker fees and grant consultancies by Astrazeneca, MSD, BMS, Roche, Novartis, Istituto Gentili, Astellas and Ipsen. Dr. Emilio Bria received speaker and travel fees from MSD, Astra-Zeneca, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche. Dr. Emilio Bria received grant consultancies by Roche and Pfizer. Dr. Marcello Tiseo received speaker fees and grant consultancies by Astrazeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda and Pierre Fabre. Dr. Alessandro Morabito received speaker fees by Astra, Roche, BMS, MSD, Boehringer, Pfizer, Takeda. Dr. Francesca Mazzoni received grant consultancies by MSD and Takeda. Dr. Raffaele Gisti received speaker fees and grant consultancies by Astrazeneca and Roche. Dr. Francesco Passiglia received grant consultancies by MSD and Astrazeneca. Dr. Paolo Bironzo received grant consultancies by Astrazeneca and Boehringer-Ingelheim. Dr. Alex Friedlaender received grant consultancies by Roche, Pfizer, Astellas and BMS. Dr. Alfredo Addeo received grant consultancies by Takeda, MSD, BMJ, Astrazeneca, Roche and Pfizer. Dr. Rita Chiari received speaker fees by BMS, MSD, Takeda, Pfizer, Roche and Astrazeneca. Dr. Carlo Genova received speaker fees/grant consultancies by Astrazeneca, BMS, Boehringer-Ingelheim, Roche and MSD.
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All patients provided written, informed consent to treatment with immunotherapy. The procedures followed were in accordance with the precepts of Good Clinical Practice and the declaration of Helsinki. The study was approved by the respective local ethical committees on human experimentation of each institution, after previous approval by the coordinating center (Comitato Etico per le provice di L’Aquila e Teramo, verbale N.15 del 28 Novembre 2019).
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Table 1:
Patients characteristics. *Available for 731 patients (67.3%). # Available for 128 out of 181 (70.7%) palliative radiation treatments. ¥ Available for 35 out of 47 (74.5%) non-palliative radiation treatments. NA: not available (DOC 63 kb)
Table 2:
Correlation analyses between previous RT categories, baseline steroids and sites of metastases. # χ2 test for trend. (DOC 38 kb)
Supplementary file 3:
List of the oncological institution of the study (PDF 155 kb)
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Cortellini, A., Tiseo, M., Banna, G.L. et al. Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%. Cancer Immunol Immunother 69, 2209–2221 (2020). https://doi.org/10.1007/s00262-020-02613-9
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DOI: https://doi.org/10.1007/s00262-020-02613-9