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, Lee Jia, Qianzhi Wang, Liyu Liu, Yan Xu, Li Xu, Yi Wen Kong, Kang Li, Fang Xu, Shuzhi Liang, Andrés F. Cardona, Lin Wu
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.