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.

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+versusIC- metastatic LCNEC, the former had significantly longer progression-free survival [9 (4-13)versus4 (1-8) months;p = 0.03], with a trend towards better median OS [12 (7-18)versus9.5 (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)versus11 (8-18) months, respectively]. Median OS was significantly shorter for patients with TC+/IC- metastatic LCNECs than those with TC-IC+ lesions (2versus8 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.