2165 - Incidence and Risk Factors for Pneumonitis Associated with Checkpoint Inhibitors and Chemotherapy in Extensive-Stage Small Cell Lung Cancer

Y. Yao, B. Li, R. Song, L. Yang, B. Zou, and L. Wang; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China

Purpose/Objective(s): Immune checkpoint inhibitors (ICIs) in combination with chemotherapy are the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). Improved efficacy was observed for ES-SCLC receiving chemotherapy and ICIs with the addition of radiotherapy. Due to its high incidence and lethality, radiotherapy-immunotherapy related pneumonitis needs considerable clinical attention. However, risk factors for pneumonitis in ES-SCLC patients (pts) are unclear. This study aims to analyze the incidence and outcome of pneumonitis in ES-SCLC pts treated with first-line ICIs and chemotherapy by real-world data, and to explore the risk factors for the development of pneumonitis. Materials/

Methods: ES-SCLC pts who received chemotherapy and ICIs as first-line therapy from three hospitals were included in the analysis between July 2018 and January 2023. Clinical characteristics, treatment parameters, the occurrence of pneumonitis, and survival-related data of the enrolled pts were retrospectively collected. Progression-free survival (PFS) was defined as the time from the first treatment to disease progression or death or last follow-up, and overall survival (OS) was defined as the time from the first treatment to death from any cause or last follow-up. The diagnosis of pneumonitis was determined by the senior doctors and confirmed by the radiologist. Cox regression was used to analyze the cumulative risk factors for the development of pneumonitis. Kaplan-Meier method was used to analyze the correlation between the development of pneumonitis and the PFS and OS.
Results: A total of 276 pts were enrolled in the analysis, and 118 of them received thoracic radiotherapy. The median follow-up time was 22.3 months. There were 41 pts (14.9%) who developed pneumonitis during follow-up, of which 22% were high-grade (grade = 3) pneumonitis. The most common initial symptom was cough (87.8%), shortness of breath (46.3%) and fever (22%). Of which, 82.9% pts with pneumonitis were treated with steroid, 9.8% pts had mild symptoms and did not receive any drug intervention, and the rest 7.3% received steroid plus anti-pulmonary fibrosis drugs (e.g., nidanib and pirfenidone). Eventually, 29 pts (70.7%) experienced resolution of the pneumonitis (including complete response and partial response). Univariate and multivariate Cox analysis indicated that TRT (HR = 2.52, 95% CI: 1.33-4.76) and history of interstitial lung disease (ILD) (HR = 8.29, 95% CI: 2.93-23.44) were independent risk factors for the development of pneumonitis. Survival analysis showed that the occurrence of pneumonitis was not significantly associated with PFS (mPFS 10.37 vs 8.87, P=0.97) and OS (mOS 19.23 vs 16.83, P=0.97).
Conclusion: The incidence of pneumonitis was tolerable in ES-SCLC pts who received ICIs and chemotherapy with the incidence of 14.9%, and most pts experienced resolution. Patients who received TRT or with a history of ILD were associated with higher risk of pneumonitis and need more vigilance.