Efficacy of immune checkpoint inhibitors in non-small cell lung cancer: A systematic review and meta-analysis
Fang Yang1, Yucai Wang2, Lin Tang3
1The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, China.
Background:
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients benefit from ICIs, and whether the magnitude of benefit is specific factor-dependent remains unclear. We performed a systematic review to improve our understanding of clinicopathologic and biomolecular features associated with improved survival upon treatment with ICIs for NSCLC.
Methods:
We searched PubMed, Web of Science, Embase, and Scopus from database inception to August 31, 2021, for randomized controlled trials (RCTs) comparing overall survival (OS) in NSCLC treated with ICIs vs control therapies. We calculated the pooled OS hazard ratio (HR) and 95% CI in subgroups using a random-effects model, and assessed the heterogeneity between the paired estimates using an interaction test.
Results:
A total of 23 RCTs involving 15,829 patients were included. We found that wild-type EGFR, high PD-L1 expression, and high bTMB were associated with a significant OS benefit from ICIs, but not mutant EGFR, low PD-L1 expression, and low bTMB. The differences of OS benefit between wild-type and mutant EGFR (HR=1.53, 95%CI 1.13-2.08), high and low PD-L1 (HR=1.35; 95%CI 1.14-1.61), high and low bTMB (HR=1.71; 95%CI 1.17-2.52) were statistically significant. OS benefit was found in all subgroups regardless of sex, age, ECOG PS, histology, smoking history, baseline brain metastasis, race, and region, and the interaction test demonstrated no significant difference of the OS benefit between these opposed subgroups (e.g. male vs female).
Conclusions:
Wild-type EGFR, high PD-L1 expression, and high bTMB are associated with a greater magnitude of efficacy from ICIs vs control therapies in NSCLC. However, the administration of ICIs should not be restricted to other clinicopathological factors (sex, smoking history, race, etc.).
Insights
Immune checkpoint inhibitors (ICIs) improve survival in non-small cell lung cancer (NSCLC) for patients with wild-type EGFR, high PD-L1, or high tumor mutational burden. Other factors like sex or age did not significantly alter ICI efficacy.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) show promise in non-small cell lung cancer (NSCLC).
- Predicting patient response to ICIs remains a challenge.
- Understanding factors influencing ICI efficacy is crucial for personalized treatment.
Approach:
- Systematic review of 23 randomized controlled trials (RCTs) involving 15,829 NSCLC patients.
- Analyzed overall survival (OS) in subgroups based on clinicopathologic and biomolecular features.
- Calculated pooled hazard ratios (HR) and 95% confidence intervals (CI) using random-effects models.
Key Points:
- Wild-type EGFR, high PD-L1 expression, and high tumor mutational burden (bTMB) significantly correlate with improved OS benefit from ICIs.
- Mutant EGFR, low PD-L1, and low bTMB did not show a significant OS benefit.
- Statistically significant differences in OS benefit were observed between wild-type and mutant EGFR (HR=1.53), high and low PD-L1 (HR=1.35), and high and low bTMB (HR=1.71).
Conclusions:
- Wild-type EGFR, high PD-L1, and high bTMB are key predictors of enhanced efficacy with ICIs in NSCLC.
- ICI treatment benefits were observed across various demographic and clinical subgroups, including sex, age, and smoking history.
- ICI administration should not be limited based on these other clinicopathological factors.
