Therapeutic Advances in Medical Oncology (Jul 2020)

PD-L1-expression patterns in large-cell neuroendocrine carcinoma of the lung: potential implications for use of immunotherapy in these patients: the GFPC 03-2017 “EPNEC” study

  • Dominique Arpin,
  • Marie-Christine Charpentier,
  • Marie Bernardi,
  • Isabelle Monnet,
  • Aurelie Boni,
  • Emmanuel Watkin,
  • Isabelle Goubin-Versini,
  • Régine Lamy,
  • Laurence Gérinière,
  • Margaux Geier,
  • Fabien Forest,
  • Radj Gervais,
  • Anne Madrosyk,
  • Florian Guisier,
  • Cécile Serrand,
  • Chrystèle Locher,
  • Chantal Decroisette,
  • Pierre Fournel,
  • Jean-Bernard Auliac,
  • Thierry Jeanfaivre,
  • Jacques Letreut,
  • Hélène Doubre,
  • Geraldine Francois,
  • Nicolas Piton,
  • Christos Chouaïd,
  • Diane Damotte

DOI
https://doi.org/10.1177/1758835920937972
Journal volume & issue
Vol. 12

Abstract

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Background: Few data are available on programmed cell-death-protein-1–ligand-1 (PD-L1) expression on large-cell neuroendocrine carcinomas of the lung (LCNECs). We analyzed PD-L1 expression on tumor (TCs) and inflammatory cells (ICs) from LCNEC patients to assess relationships between this expression, clinical characteristics, and disease outcomes. Methods: PD-L1 expression was determined by immunohistochemistry with monoclonal antibody 22C3 in consecutive LCNEC patients managed in 17 French centers between January 2014 and December 2016. Results: After centralized review, only 68 out of 105 (64%) patients had confirmed LCNEC diagnoses. Median overall survival (OS) (95% CI) was 11 (7–16) months for all patients, 7 (5–10), 21 (10–not reached) and not reached months for metastatic, stage III and localized forms ( p = 0.0001). Respectively, 11% and 75% of the tumor samples were TC+ and IC+, and 66% had a TC–/IC+ profile. Comparing IC+ versus IC– metastatic LCNEC, the former had significantly longer progression-free survival [9 (4–13) versus 4 (1–8) months; p = 0.03], with a trend towards better median OS [12 (7–18) versus 9.5 (4–14) months; p = 0.21]. Compared to patients with TC– tumors, those with TC+ LCNECs tended to have non-significantly shorter median OS [4 (1–6.2) versus 11 (8–18) months, respectively]. Median OS was significantly shorter for patients with TC+/IC– metastatic LCNECs than those with TC–IC+ lesions (2 versus 8 months, respectively; p = 0.04). Conclusion: TC–/IC+ was the most frequent PD-L1–expression profile for LCNECs, a pattern quite specific compared with non-small-cell lung cancer and small-cell lung cancer. IC PD-L1 expression seems to have a prognostic role.