Abstract 1100P
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
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
Squamous NSCLC derived significantly larger survival benefit from ICI than non-squamous NSCLC. Tumour mutation burden (TMB) and programmed death ligand 1 (PD-L1) expression were confirmed to be predictors of response to ICI. ICI had significantly lower efficacy in EGFR-mutated NSCLC while KRAS-mutated NSCLC showed higher efficacy. Men or smokers derived significantly larger benefit from ICI alone compared with women or non-smokers, while sex and smoking status didn't affect the efficacy of ICI-based combination treatments. Table: 1100P
| Subgroup A vs Subgroup B | HRR (Progression-free Survival) | |
| ICI monotherapy | ICI-based combination treatments | |
| Squmaous vs Non-squmaous NSCLC | 0.76 (0.65-0.88) | 0.82 (0.70-0.96) |
| Patients ≧65 y vs Patients <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 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.