Abstract 337P
Background
Immune checkpoint inhibitors (ICI) have revolutionized the management of non-small cell lung cancer (NSCLC), while only a small proportion of patients respond. We assessed the association of clinical or molecular factors with the efficacy of ICI given either alone (ICI alone) or combined with other treatments (ICI-based combination treatments).
Methods
Systematic searches of PubMed, Embase, Scopus, and Cochrane Library databases was conducted from inception to October 16, 2021. Abstracts and presentations from all major conferences were also reviewed. All randomized clinical trials that compared ICI with chemotherapy and have data available for hazard ratio (HR) were included. The primary objective was the association of the investigated factors with the efficacy of ICI. To assess the association, first, a trial-specific ratio of HRs [HRR=(HR in subgroup A)/(HR in subgroup B)] was calculated; second, these HRRs were combined to obtain a pooled HRR. A pooled HRR lower than 1 indicates a greater efficacy in subgroup A.
Results
In total, 42 trials involving 24645 patients were included in the meta-analysis. Squamous NSCLC derived significantly larger survival benefit from both ICI alone and ICI-based combination treatments than non-squamous NSCLC. Tumour mutation burden (TMB) and programmed death ligand 1 (PD-L1) expression were confirmed to be predictors of response to both ICI alone and ICI-based combination treatments. The efficacy in patients with higher levels of TMB or PD-L1 expression was larger than that in patients with lower levels. ICI alone and ICI-based combination treatments had significantly lower efficacy in EGFR-mutated NSCLC compared with wild-type NSCLC while KRAS-mutated NSCLC showed higher efficacy than wild-type NSCLC. Men or smokers derived significantly larger benefit from ICI alone compared with women or non-smokers, respectively. However, there was no association between the efficacy of ICI-based combination treatments and sex or smoking status. Besides, age and performance status did not significantly influence the efficacy of ICI. Table: 337P
| Subgroup A vs B | HRR | |
| Progression-free Survival (ICI monotherapy) | Progression-free Survival (ICI-based combination treatments) | |
| Squamous vs Non-squamous | 0.76 (0.65-0.88) | 0.82 (0.70-0.96) |
| ≧65 y vs <65 y | 1.04 (0.90-1.21) | 1.12 (0.98-1.27) |
| Male vs Female | 0.70 (0.59-0.82) | 1.02 (0.88-1.17) |
| Smoker vs Non-smoker | 0.60 (0.46-0.80) | 0.84 (0.69-1.01) |
| EGOG PS≧1 vs EGOG PS=0 | 0.86 (0.73-1.01) | 1.07 (0.94-1.22) |
| EGFR-mutated vs EGFR wild-type | 1.47 (1.14-1.90) | 1.47 (1.14-1.90) |
| KRAS-mutated vs KRAS wild-type | 0.77 (0.61-0.96) | 0.77 (0.61-0.96) |
| PD-L1 ≧1% vs PD-L1 <1% | 0.77 (0.65-0.92) | 0.81 (0.73-0.89) |
| PD-L1 ≧50% vs PD-L1 <50% | 0.56 (0.47-0.65) | 0.67 (0.59-0.77) |
| High-TMB vs Low-TMB | 0.58 (0.48-0.68) | 0.58 (0.47-0.71) |
Conclusions
Histology, PD-L1 expression, TMB and mutation status of EGFR and KRAS have an impact on the efficacy of both ICI monotherapy and ICI-based combination treatments while sex and smoking status only affect the efficacy of ICI monotherapy. These factors should be taken into account in future clinical trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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