PD-L1 Inhibitors Combined with Thoracic Radiotherapy in First-Line Treatment of Extensive Stage Small Cell Lung Cancer: A Propensity Score-Matched, Real-World Study

Abstract

The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival of extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy is controversial. This study aims to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. Thepatients who received PD-L1 inhibitors combined with platinum-based chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were retrospectively collected. According to whether they received TRT, they were divided into two groups, and the follow-up analysis was performed. Propensity score matching (PSM) in with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were progression-free survival (PFS) and OS. A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 65 pairs of patients were enrolled in the analysis. There were no significant differences in baseline characteristics between the two groups of patients who received TRT and those who did not. In all patients, the median PFS (mPFS) in the TRT group and the non-TRT groupwere 9.5 months and 7.2 months, respectively, with HR = 0.60 (95% CI 0.41-0.87, p = 0.007). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95% CI 0.32-0.85, p = 0.009). Multivariable analysis showed that baseline liver metastasis and bone metastasis were independent prognostic factors for OS. In terms of safety, immunotherapy combined with thoracic radiotherapy increased the incidence of treatment-related pneumonia (p<0.001), most of which were grade 1-2. This real-world study shows that adding TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. It leads to more treatment-related pneumonia, but most of them can be relieved after symptomatic treatment. This treatment model deserves to be explored in prospective clinical trials.