Neoadjuvant treatment does not influence PD-L1 expression in stage III non-small-cell lung cancer: a retrospective analysis of tumor samples from the trials SAKK 16/96, 16/00, 16/01, and 16/14

Abstract

Background: The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression.

Patients and methods: We assessed PD-L1 expression by immunohistochemistry (Ventana SP263 assay) on tumor cells in treatment-naive diagnostic tumor samples and matched lung resections from patients with stage III non-small-cell lung cancer included in the Swiss Group for Clinical Cancer Research (SAKK) trials 16/96, 16/00, 16/01, and 16/14. All patients received neoadjuvant chemotherapy (CT) with cisplatin/docetaxel, either as single modality (CT), with sequential radiotherapy [chemoradiation therapy (CRT)] or with the PD-L1 inhibitor durvalumab (CT + ICI).

Results: Overall, 132 paired tumor samples were analyzed from patients with neoadjuvant CT (n = 69), CRT (n = 33) and CT + ICI (n = 30). For CT and CRT, PD-L1 expression before and after neoadjuvant treatment did not differ significantly (Wilcoxon test, P = 0.94). Likewise, no statistically significant difference was observed between CT and CRT for PD-L1 expression after neoadjuvant treatment (P = 0.97). For CT + ICI, PD-L1 expression before and after neoadjuvant treatment also did not differ significantly (Wilcoxon test, P > 0.99). Event-free survival and overall survival for patients with downregulation or upregulation of PD-L1 expression after neoadjuvant treatment were similar.

Conclusions: In our cohort of patients neoadjuvant treatment did not influence PD-L1 expression, irrespective of the specific neoadjuvant treatment protocol. Dynamic change of PD-L1 expression did not correlate with event-free survival or overall survival.

Keywords: PD-L1 expression; chemoradiation; immune checkpoint inhibitor; non-small-cell lung cancer; predictive biomarker.

Figure 1

Study overview. PD-L1, programmed death-ligand 1; SAKK, Swiss Group for Clinical Cancer Research.

Figure 2

Median programmed death-ligand 1 (PD-L1) expression [tumor proportion score (TPS)] in preneoadjuvant and postneoadjuvant treatment samples. (A) Chemotherapy (CT) and chemoradiation therapy (CRT), (B) CT only, (C) CRT only, (D) CT + immune checkpoint inhibitor.

Figure 3

Example of a preneoadjuvant treatment sample [A; cell block, transbronchial fine-needle aspiration from lymph node, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) 100%] and a postneoadjuvant treatment sample (B; primary tumor/resection specimen, PD-L1 TPS 100%).

Figure 4

Overall survival and event-free survival of patients in the (A, B) chemotherapy and chemoradiation therapy (CT + CRT) cohort and (C, D) CT + immune checkpoint inhibitor (ICI) cohort (C, D) whose tumors had stability, upregulation, or downregulation of programmed death-ligand 1 expression after neoadjuvant treatment.