Real-World Study of Overall Survival in Patients with Stage III Non-Small Cell Lung Cancer Treated with Chemoradiotherapy with or without Durvalumab and an Exploratory Analysis of Effective Radiation Dose to the Immune Cells

Abstract

To investigate the real-world data on overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) with or without consolidation durvalumab, and to perform an exploratory analysis on effective radiation dose to the immune cells (EDIC). In our multi-institutional retrospective study, patients who received CCRT between July 2018 and July 2019 for stage III NSCLC in Japan were investigated. EDIC was estimated using mean lung dose, mean heart dose, body volume, body mean dose, and body weight, as reported in the secondary analysis of RTOG 0617. The cut-off value of EDIC was calculated using the maximally selected log-rank statistics. One hundred and seventy-eight patients were eligible for the analysis (136 patients, CCRT with consolidation durvalumab [CCRT+D] cohort; 42 patients, CCRT cohort). The median follow-up period was 42.5 months. Three-year OS rates were 59.8% in the overall cohort: 60.5% in the CCRT+D cohort, and 58.0% in the CCRT cohort with no significant difference (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.45-1.27; P = 0.29). Univariate analysis showed that ECOG-PS, smoking history, histology, EGFR mutational status, gross tumor volume and EDIC were significantly associated with OS. Multivariate analysis showed that ECOG-PS 2, gross tumor volume ≥ 57 cm3 and EDIC ≥ 4.4 Gy were associated with poor OS. Among 21 EGFR-mutated patients, 3 year-OS rates were 64.7% in the CCRT+D cohort and 100% in the CCRT cohort, while 3 year-OS rates were 68.8% and 58.7% among 90 EGFR wild-type patients. Three-year OS rates were 64.6% and 47.6% for EDIC < 4.4 Gy and EDIC ≥ 4.4 Gy in the overall cohort (HR, 1.82; 95% CI, 1.14-2.90; P = 0.015). In the subgroup analysis, 66.3% vs. 44.4% in the CCRT+D cohort (HR, 2.01; 95% CI, 1.17-3.47; P = 0.016), and 59.0% vs. 56.1% in the CCRT cohort (HR, 1.20; 95% CI, 0.48-3.01; P = 0.70), respectively. Our real-world data in Japan showed that there was no significant difference in OS between the CCRT+D cohort and the CCRT cohort. High EDIC could be a risk for poor OS in patients treated with CCRT and consolidation durvalumab compared with those treated with CCRT.