The influence of baseline characteristics on the efficacy of immune checkpoint inhibitors for advanced lung cancer: A systematic review and meta-analysis

Abstract

Purpose: To investigate the impact of different baseline characteristics on the efficacy of immune checkpoint inhibitors (ICIs) for advanced lung cancer.Methods: In order to identify eligible randomized controlled trials (RCTs), a systematic search was conducted in PubMed, Embase, Web of Science, and Scopus Cochrane Library databases. The primary outcomes were hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). To explore the potential interaction during the administration of ICI, patients were stratified by baseline characteristics.Results: The meta-analysis included 24 RCTs. ① Compared with non-ICI therapy, patients with lung cancer benefitted more from immunotherapy (HR, 0.78; p < 0.0001). ② Patients without liver metastases could get more survival benefits than those with liver metastases (HR, 1.20; p = 0.0139). Similar outcomes were also observed in the following subgroups: small-cell lung cancer (HR, 1.20; p = 0.0433), subsequent line (HR, 1.40; p = 0.0147), and ICI monotherapy (HR, 1.40; p = 0.0147). ③ Subgroup analysis showed that tumor type affected the efficacy of immunotherapy in patients with brain metastases (HR, 0.72 vs. 1.41; interaction, p < 0.01). Among patients with smoking history (HR, 0.87 vs. 1.23; interaction, p = 0.05) and brain metastases (HR, 0.69 vs. 1.21; interaction, p = 0.05), the type of therapy (i.e., monotherapy or combination therapy) had potential influences on the efficacy of immunotherapy.Conclusion: Some critical baseline characteristics could indicate the efficacy of ICI therapy. Liver metastasis status could predict the efficacy of ICI therapy for lung cancer. Compared with small-cell lung cancer, patients with brain metastases might have durable OS in non-small-cell lung cancer. The smoking history or brain metastasis status of patients could indicate the potential clinical benefits of monotherapy or combination therapy.

Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

“…As demonstrated in other cohort studies and RCTs, the presence of liver metastases was negatively associated with DCB and OS [ 44 , 45 , 46 ]. A study of patients with malignant melanoma showed that liver metastases had significantly lower T-cell infiltration and increased TIM-3 expression than lung and lymph node metastases [ 47 ].…”

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB−IV non‐small cell lung cancer

“…Previous studies on the impact of smoking on OS of immunotherapy have produced conflicting results. 55,56 A meta-analysis by Xiao et al 56 suggested that non-smokers with advanced lung cancer benefit more from ICIs combination therapy, while smokers benefit more from ICIs monotherapy. Notably, our statistical analysis did not find significant differences in the incidence of irAEs between stroma-L and stroma-H groups, suggesting that iTSP does not impact the safety of ICIs treatment.…”

“…We also observed that past or current smoking was independently associated with worse survival compared to never smoking. Previous studies on the impact of smoking on OS of immunotherapy have produced conflicting results 55,56 . A meta‐analysis by Xiao et al 56 .…”

“…Previous studies on the impact of smoking on OS of immunotherapy have produced conflicting results 55,56 . A meta‐analysis by Xiao et al 56 . suggested that non‐smokers with advanced lung cancer benefit more from ICIs combination therapy, while smokers benefit more from ICIs monotherapy.…”

Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis

“…The overall effectiveness and safety of immunotherapy utilizing ICIs have been generally demonstrated in patients afflicted with metastatic and locally advanced non-small cell lung cancer (NSCLC) (8), as well as small cell lung cancer (SCLC) (9). However, subsequent observations suggest that the therapeutic response to ICIs may vary in individual patients with lung cancer (10). Accordingly, uncovering of the clinical factors that are related to the efficacy of ICIs in patients with lung cancer is of great clinical significance.…”