Abstract
Background PD-1/PD-L1 immune checkpoint inhibitors have been approved for monotherapy of metastatic non-small cell lung cancer (mNSCLC) depending on tumor cells' PD-L1 expression. Pleural effusion (PE) is common in mNSCLC. The significance of immunocytochemistry PD-L1 analysis from PE samples is unclear.
Aim of the study To analyse the sensitivity regarding immunocytochemistry PD-L1 analysis of PE in NSCLC as compared to immunohistochemistry of pleural biopsies.
Patients and Methods 50 consecutive subjects (17 female, median age 72.5, 7 never-smokers) were enrolled in this prospective controlled two-center study. Inclusion criteria were PE, suspected or known lung cancer, indication for pleural puncture and thoracoscopy, written informed consent. Immunocytochemistry and immunohistochemistry PD-L1 analyses were performed with the Dako-PDL1-IHC-22C3pharmDx assay. Analysis for sensitivity, specificity, positive (PPV) and negative predictive value (NPV) was performed for PD-L1 detection from PE.
Results 50 subjects underwent pleural puncture and thoracoscopy. Pathologic diagnoses were lung cancer (48), lymphoma (1), mesothelioma (1). Sensitivity, specificity, positive-predictive-value and negative-predictive-value of PD-L1-testing with expression ≥50% defined as positive were 100% (95% confidence interval 46–100%), 63%(36–84%), 45%(18–75%), 100%(66–100%), and with expression ≥1% defined as positive 86%(56–97%), 43%(12–80%), 75%(47–92%), 60%(17–93%).
Conclusion PD-L1 analysis in tumor-positive PE samples shows a very high sensitivity and negative-predictive-value, especially regarding PD-L1 expression levels ≥50% (European Medicines Agency approval). Negative results are reliable and help in the decision against a first-line checkpoint inhibitor monotherapy. However, a 1% cut-off level (United States Food and Drug Administration approval) leads to a markedly lower negatve-predictive-value, making other invasive procedures necessary. (NCT02855281)
Footnotes
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Conflict of interest: Dr. Hagmeyer reports grants from MSD Sharp & Dohme GmbH, Haar, Germany, during the conduct of the study; grants from AstraZeneca, from Roche, from Boehringer Ingelheim, from Pfizer, outside the submitted work.
Conflict of interest: Dr. Schäfer reports personal fees from Boehringer Ingelheim, personal fees from BMS, outside the submitted work.
Conflict of interest: Dr. Engels has nothing to disclose.
Conflict of interest: Dr. Pietzke-Calcagnile has nothing to disclose.
Conflict of interest: Dr. Treml has nothing to disclose.
Conflict of interest: Dr. Herkenrath has nothing to disclose.
Conflict of interest: Dr. Heldwein has nothing to disclose.
Conflict of interest: Dr. Hekmat has nothing to disclose.
Conflict of interest: Dr. Matthes has nothing to disclose.
Conflict of interest: Dr. Scheel has nothing to disclose.
Conflict of interest: Dr. Wolf reports personal fees from Abbvie, personal fees from AstraZeneca, personal fees from Blueprint, grants and personal fees from BMS, personal fees from Böhringer, from Chugai, personal fees from Ignyta, grants and personal fees from Jannsen, personal fees from Lilly, personal fees from Loxo, grants and personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from Pfizer, personal fees from Roche, personal fees from Takeda, from null, outside the submitted work.
Conflict of interest: Dr. Buettner has nothing to disclose.
Conflict of interest: W. Randerath reports speaking fees and travel grants from Philips Respironics, Heinen and Löwenstein, Resmed, Bayer Vital, Bioprojet, and Vanda Pharma, outside the submitted work.
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- Received November 1, 2020.
- Copyright ©ERS 2020
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