2175 - Benefit of Thoracic Radiotherapy Following First-Line Chemoimmunotherapy in ES-SCLC: Stratified by Clinical and Therapeutic Characteristics

J. Wu¹, J. Li², S. Wang², J. Zhang³, H. Sun³, Y. Ge⁴, Q. Cheng⁵, Y. Sun⁶, D. Wang², X. Fu³, Y. Sun², and A. Gao⁷; ¹Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, jinan, shand, China, ²Shandong Cancer Hospital And Institute,Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ShanDong, China, ³Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, jinan, shandong, China, ⁴Shandong University Cancer Center, Jinan, Shandong, China, ⁵Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, jinan, China, ⁶Phase I Clinical Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117,Shandong Province, China., Jinan 250117,Shandong Province, China, China, ⁷Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China

Purpose/Objective(s): PD-1/PD-L1 inhibitors combined with chemotherapy have become the standard first-line options in extensive stage small-cell lung cancer (ES-SCLC). However, whether consolidative thoracic radiotherapy (TRT) following first-line chemoimmunotherapy can further improve patient outcome is still controversial. More importantly, the subpopulation who can benefit from TRT is unknown.

Materials/

Methods: ES-SCLC patients who received standard first-line chemoimmunotherapy with/without subsequent TRT were included from 3 cancer centers in China between February 2020 to September 2023. The clinical outcomes and safety were evaluated.

Results: 258 ES-SCLC patients were eligible for our analysis, in which 158 received TRT and maintenance PD-(L)1 inhibitors after chemotherapy, and 100 received maintenance PD-(L)1 inhibitors alone. TRT significantly prevented the intrathoracic lesion progression (12.5% vs 62.5%), improved the progression-free survival (PFS) (median 10.67 vs 8.37 months, HR=0.63[95% CI: 0.45-0.87], p=0.002) and locoregional recurrence-free survival (LRFS) (median 27.27 vs 14.67 months, HR=0.47[95% CI: 0.31-0.71], p <0.001). However, TRT did not bring a benefit on overall survival (OS). Further analysis on clinical characteristics revealed that patients with female gender, with 2 or fewer metastases, or without liver, bone or adrenal metastases were more likely to benefit from TRT. In terms of therapeutic features, we found different biological effective dose or dose fractionation mode of radiotherapy didn’t impact PFS benefit of TRT. However, administration of TRT within 3-6 weeks after chemotherapy markedly prolonged PFS compared with TRT upon intrathoracic disease progression (median PFS 10.93 vs 8.27 months, HR=0.36[95% CI: 0.13-1.00], p=0.001). In addition, patients receiving PD-L1 inhibitors showed more significant PFS prolongation in relative to those receiving PD-1 inhibitors. TRT slightly increased =grade 3 adverse effect (33.54% vs 24.00%). Notably, the incidence of pneumonia was markedly higher in the TRT group than in the maintenance immunotherapy group (23.40% vs 8.00%).

Conclusion: The addition of TRT after first-line chemoimmunotherapy improves local control rate, PFS and LRFS in ES-SCLC patients. Female, patients with =2 metastases and without liver, bone or adrenal metastases, seems to benefit more from TRT. TRT should be performed within 3-6 weeks after chemotherapy. The application of TRT is generally safe excepted for increased pneumonia occurrence.