Efficacy of radiotherapy combined with atezolizumab or docetaxel in patients with previously treated NSCLC

Junzhu Xu; Haitao Wang; Chi Zhang; Su-Han Jin; Xiaofei Chen; Fangya Tan; Benjamin Frey; Markus Hecht; Jian-Guo Sun; Udo S Gaipl; Hu Ma; Jian-Guo Zhou

doi:10.1016/j.isci.2024.111363

Efficacy of radiotherapy combined with atezolizumab or docetaxel in patients with previously treated NSCLC

iScience. 2024 Nov 8;27(12):111363. doi: 10.1016/j.isci.2024.111363. eCollection 2024 Dec 20.

Authors

Junzhu Xu¹, Haitao Wang², Chi Zhang¹, Su-Han Jin³, Xiaofei Chen⁴, Fangya Tan⁵, Benjamin Frey^{6

7

8}, Markus Hecht⁹, Jian-Guo Sun¹⁰, Udo S Gaipl^{6

7

8}, Hu Ma¹, Jian-Guo Zhou^{1

6

7

8}

Affiliations

¹ Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi 563000, P.R. China.
² Thoracic Surgery Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
³ Department of Orthodontics, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China.
⁴ Oncology Biometrics, AstraZeneca, Gaithersburg, MD 20850, USA.
⁵ Harrisburg University of Science and Technology, Harrisburg, PA 17101, USA.
⁶ Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
⁷ Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
⁸ FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-Alexander- Universität Erlangen-Nurnberg, Erlangen, Germany.
⁹ Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center, Homburg, Germany.
¹⁰ Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China.

Abstract

Radiotherapy showed synergy with immunotherapy, yet the comparative effectiveness of combining immunotherapy (iRT) or chemotherapy (CRT) after platinum therapy failure in advanced non-small cell lung cancer (NSCLC) remains unexplored. We analyzed 163 patients (iRT: n = 120 vs. CRT: n = 43) eligible for combination radiotherapy. Before matching, median overall survival (OS) was significantly longer in iRT group (7.79 vs. 4.57 months, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41-0.94, p = 0.024). After 1:2 propensity score matching (PSM) and inverse probability of treatment weighting (IPTW), iRT group showed improved OS, consistent with unmatched analysis (PSM, p = 0.033 and IPTW, p = 0.035). Exploratory analysis suggested that PD1⁺, central memory PD1⁺, and effector memory PD-L1⁺ CD4⁺ T cells were strong predictive biomarkers for iRT-treated patients (P _OS = 0.025, P _OS = 0.002, P _OS = 0.010, respectively). Proliferative CD4⁺ T cell_low was a prognostic (P _OS = 0.008) and predictive biomarker for iRT (P _OS < 0.001). Our work revealed iRT was prolonged OS in previously treated advanced NSCLC patients. Additionally, proliferative CD4⁺ T cell served as prognostic and predictive biomarkers.

Keywords: Cancer; Public health.