The efficacy and safety of immune checkpoint inhibitors combined with chemotherapy or anti-angiogenic therapy as a second-line or later treatment option for advanced non-small cell lung cancer: a retrospective comparative cohort study

Bolin Chen; Jingyi Wang; Xingxiang Pu; Jia Li; Qianzhi Wang; Liyu Liu; Yan Xu; Li Xu; Yi Kong; Kang Li; Fang Xu; Shuzhi Liang; Andrés F Cardona; Lin Wu

doi:10.21037/tlcr-22-697

The efficacy and safety of immune checkpoint inhibitors combined with chemotherapy or anti-angiogenic therapy as a second-line or later treatment option for advanced non-small cell lung cancer: a retrospective comparative cohort study

Transl Lung Cancer Res. 2022 Oct;11(10):2111-2124. doi: 10.21037/tlcr-22-697.

Authors

Bolin Chen^#¹, Jingyi Wang^#¹, Xingxiang Pu¹, Jia Li¹, Qianzhi Wang¹, Liyu Liu¹, Yan Xu¹, Li Xu¹, Yi Kong¹, Kang Li¹, Fang Xu¹, Shuzhi Liang¹, Andrés F Cardona^{2

3

4}, Lin Wu¹

Affiliations

¹ The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
² Foundation for Clinical and Applied Cancer Research-FICMAC, Bogotá, Colombia.
³ Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad el Bosque, Bogotá, Colombia.
⁴ Direction of Research and Education, Luis Carlos Sarmiento Angulo Cancer Treatment and Research Cencer-CTIC, Bogotá, Colombia.

^# Contributed equally.

Abstract

Background: Although immune checkpoint inhibitor (ICI) monotherapy remains the standard of second-line treatment for patients with advanced non-small cell lung cancer (NSCLC) , the objective response rate (ORR) is low. There is an urgent need to increase the response population of second-line immunotherapy, and ICI combination therapy may be a possible option. However, the evidence is insufficient.

Methods: We retrospectively collected the medical records of patients who received ICI monotherapy or ICI combination therapy as a second-line or later treatment option. We further analysed baseline clinical characteristics, evaluated treatment efficacy, assessed treatment-related adverse events (AEs) and followed up survival. The outcome variables assessed in the study were ORR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs.

Results: A total of 145 patients were ultimately enrolled in this study, including the ICI monotherapy group (n=63) and ICI combination therapy group (n=82). The ICI combination therapy group was further divided into the ICI/chemotherapy group (n=57) and ICI/anti-angiogenic therapy group (n=25). The baseline was comparable among the three subgroups. The ICI combination therapy groups showed a higher ORR (29.3% vs. 11.1%, P=0.008) and DCR (85.4% vs. 61.9%, P=0.001) and a longer PFS (6.77 vs. 3.47 months, P<0.001) and OS (18.60 vs. 8.47 months, P<0.001) than the ICI monotherapy group. The ICI/chemotherapy group showed a significantly higher ORR (31.6% vs. 11.1%, P=0.006) and DCR (84.2% vs. 61.9%, P=0.006) and a longer PFS (6.37 vs. 3.47 months, P<0.001) and OS (18.60 vs. 8.47 months, P<0.001) than the ICI monotherapy group. The ICI/anti-angiogenic therapy group showed a significantly higher DCR (88.0% vs. 61.9%, P=0.021) and a longer PFS (8.17 vs. 3.47 months, P<0.001) and OS (19.20 vs. 8.47 months, P=0.005) than the ICI monotherapy group. Neither of the combined ICI therapy groups showed a significant increase in the incidence of AEs compared to the ICI monotherapy group.

Conclusions: ICI combined with chemotherapy or anti-angiogenic therapy as second-line or later treatment demonstrated superiority over ICI monotherapy in advanced NSCLC patients without prior immunotherapy. These results provide a potentially superior treatment strategy and require verification in prospective clinical trials.

Keywords: Immune checkpoint inhibitors (ICIs); anti-angiogenic therapy; chemotherapy; combined modality therapy; non-small cell lung cancer (NSCLC).