2198 - Efficacy of Radiotherapy Combined with Atezolizumab or Docetaxel in Patients with Previously Treated Non-Small-Cell Lung Cancer: A PSM-IPTW Cohort Study

J. G. Zhou^1,2, J. Xu¹, H. Wang³, C. Zhang¹, S. H. Jin⁴, X. Chen⁵, F. Tan⁶, B. Frey², M. Hecht^7,8, U. S. Gaipl², and H. Ma¹; ¹The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China, ²Department of Radiation Oncology, Universitaetsklinikum Erlangen, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany, ³Center for Cancer Research, NCI, NIH, Bethesda, MD, ⁴Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China, ⁵AstraZeneca, Gaithersburg, MD, ⁶Harrisburg University of Science and Technology, Harrisburg, PA, ⁷Comprehensive Cancer Center Erlangen-EMN,Friedrich-Alexander- Universität Erlangen-Nu¨rnberg, Erlangen, Germany, ⁸Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center, Homburg, Germany

Purpose/Objective(s): Radiotherapy holds significance in advanced non-small-cell lung cancer (NSCLC), showcasing immune-modulatory effects when integrated with systemic approaches. Despite advancements in immunotherapy, its standalone efficacy in advanced NSCLC is limited. Radiotherapy has shown synergy with immunotherapy, yet the comparative effectiveness of combining immunotherapy or chemotherapy at post-platinum therapy failure remains unexplored. Materials/

Methods: Data from four randomized clinical trials (BIRCH, FIR, POPLAR, OAK) treated with Atezolizumab or docetaxel post-platinum therapy failure were analyzed, specifically focusing on patients with locally advanced or metastatic NSCLC who underwent prior radiotherapy (RT). RT combined with immunotherapy (iRT) and chemotherapy (CRT) were defined, and clinicopathologic characteristics were considered for analysis. Propensity Score Matching (PSM) and Inverse Probability of Treatment Weighting (IPTW) methods were employed for covariate balancing. The primary endpoint was overall survival (OS), with progression-free survival (PFS) as a secondary endpoint. Exploratory Biomarker analysis to identify correlation between immune subtypes and survival.
Results: The analysis included 163 patients (iRT: n=120 vs. CRT: n=43) who met the criteria for combination radiotherapy. Prior to matching, the median OS was significantly longer in the iRT group at 7.79 months compared to 4.57 months in the CRT group (HR: 0.62, 95% CI: 0.41-0.94, P = 0.024). After 3:1 PSM and IPTW, patients treated with iRT having an improved median OS compared to patients treated with CRT, which consistent with unmatched analysis (PSM, P= 0.046 and IPTW, P= 0.035, respectively). In addition, PFS was not significantly different between two treatments. Exploratory analysis demonstrated that PD1+ CD4+ T cells and PDL1+ central memory CD4+ T cells were identified as strong predictive biomarkers for iRT-treated patients (P =0.025, P =0.003, respectively) in comparison with CRT-treated patients.
Conclusion: Our pooled analysis revealed iRT significantly prolonged OS in previously treated advanced NSCLC patients. Additionally, PD1+ CD4+ T cells and PDL1+ central memory CD4+ T cells serve as potential predictive biomarkers.