Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment

Li Liu; Tong Liu; Xingwen Wang; Jianbo Wang; Jun Wang; Meng Yuan; Yunxin Yang; Yingying Zhang; Hang Wang; Pingping Hu; Jiandong Zhang

doi:10.1016/j.tranon.2023.101687

Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment

Transl Oncol. 2023 Jul:33:101687. doi: 10.1016/j.tranon.2023.101687. Epub 2023 May 12.

Authors

Li Liu¹, Tong Liu¹, Xingwen Wang², Jianbo Wang³, Jun Wang⁴, Meng Yuan⁵, Yunxin Yang¹, Yingying Zhang⁶, Hang Wang⁷, Pingping Hu⁸, Jiandong Zhang⁹

Affiliations

¹ Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China; Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China; Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Radiotherapy, Cancer Center, Shandong Provincial Hospital, Shandong University, Jinan, China.
³ Deprtment of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
⁵ Department of Oncology, Shandong Provincial Qianfoshan Hospital, Weifang Medical University, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China.
⁶ Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China; Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China.
⁷ Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China; Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, China.
⁸ Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China; Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China; Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: hupingping0915@126.com.
⁹ Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China; Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China; Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: zhangjd2233@126.com.

Abstract

Background: Although immunotherapy greatly extends overall survival (OS) of patients with extensive-stage small cell lung cancer (ES-SCLC), a number of patients develop immunotherapy resistance (IR). Patterns of failure in ES-SCLC are not clarified. Our study aims to explore the clinical pattern of IR and prognostic factors for these patients.

Methods: The study was conducted from 117 ES-SCLC patients with immunotherapy between 2018 and 2022. Chi-square tests and Fishers' exact tests was used to explore failure patterns in different populations. Survival analyses of different progression patterns and subsequent treatment regimens were conducted by Kaplan-Meier curves and log-rank test.

Results: 86 (73.5%) patients experienced IR. The patients with smoking (never smoker vs. current or ex-smoker, 59.5 % vs. 81.3%, P = 0.010), liver metastasis (extrahepatic metastasis vs. intrahepatic metastasis, 73.6 % vs. 90.9%, P = 0.050), and distant metastasis status (no distant metastasis vs. distant metastasis, 39.1 % vs. 81.9%, P<0.001) were associated with IR rates. Liver progression had a lower incidence in 1st line immunotherapy (1st line vs. ≥2nd lines, 14.0 % vs. 41.7%, P = 0.004) and a higher incidence in multiple progression (multiple progression vs. Oligo-progression, 39.4 % vs. 17.0%, P = 0.021). Cranial (41.7 % vs. 16.1%, P = 0.012) and distant lymph node (16.7 % vs. 3.2%, P = 0.049) progression were the main failure model for acquired IR in comparison to primary IR. Patients with new lesion progression only (17.73 vs. 9.17 months, P = 0.013) and non-hepatic progression (14.23 vs. 11.67 months, P = 0.042) had a longer OS. Patients in cross-line immunotherapy after IR had a favourable prognosis (17.07 vs. 11.93 months, P = 0.007).

Conclusion: The most common failure pattern of immunotherapy for ES-SCLC was lung and regional lymph node progression. Brain and liver progression were the most common extra thoracic failure sites for 1st line and 2nd and more lines immunotherapy, respectively. There was a higher probability of primary IR in 2 lines and above immunotherapy. Patients with new only progression site and cross-line rechallenge immunotherapy had a better prognosis.

Keywords: Extensive-stage small cell lung cancer (ES-SCLC); Immunotherapy; Patterns of failure.