Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug;8(4):101595.
doi: 10.1016/j.esmoop.2023.101595. Epub 2023 Jul 11.

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

D König  1 , S Savic Prince  2 , S Hayoz  3 , P Zens  4 , S Berezowska  5 , W Jochum  6 , E Stauffer  7 , V Braunersreuther  8 , B Trachsel  3 , S Thierstein  3 , M Mark  9 , S Schmid  10 , A Curioni-Fontecedro  11 , A Addeo  12 , I Opitz  13 , M Guckenberger  14 , M Früh  15 , D C Betticher  11 , H-B Ris  16 , R Stupp  17 , S I Rothschild  18 , L Bubendorf  2 , M Pless  19
Affiliations

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

D König et al. ESMO Open. 2023 Aug.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Study overview. PD-L1, programmed death-ligand 1; SAKK, Swiss Group for Clinical Cancer Research.
Figure 2
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
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
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.
See this image and copyright information in PMC

References

    1. Reck M., Rodriguez-Abreu D., Robinson A.G., et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–1833. - PubMed
    1. Gandhi L., Rodriguez-Abreu D., Gadgeel S., et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–2092. - PubMed
    1. Paz-Ares L., Luft A., Vicente D., et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379(21):2040–2051. - PubMed
    1. Felip E., Altorki N., Zhou C., et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344–1357. - PubMed
    1. Forde P.M., Spicer J., Lu S., et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973–1985. - PMC - PubMed

Publication types