Chemo-immunotherapie ± VEGF-remming na falen van EGFR-TKI bij EGFR-gemuteerd NSCLC: meta-analyse op IPD-niveau

INTRODUCTION: Whether adding immunotherapy to chemotherapy is beneficial for some patients with EGFR-mutated NSCLC and whether concomitant vascular endothelial growth factor inhibition (VEGFi) further enhances this strategy are still subjects of debate. METHODS: We performed a systematic review and meta-analysis with reconstructed individual patient data to assess outcomes to chemo-immunotherapy with or without VEGFi in patients with advanced EGFR-mutated NSCLC after failure of EGFR tyrosine kinase inhibitors. RESULTS: Among seven randomized clinical trials (n = 2196 patients), compared with chemotherapy with or without VEGFi, chemo-immunotherapy extended the median progression-free survival whether combined with VEGFi (8.1 versus 5.5 mo; hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.53-0.67; p < 0.0001) or not (5.6 versus 5.5 mo; HR: 0.83; 95% CI: 0.74-0.93; p = 0.0017). Adding VEGFi to chemo-immunotherapy prolonged the progression-free survival even compared with chemo-immunotherapy alone (HR: 0.72; 95% CI: 0.63-0.82; p < 0.0001). Similarly, median overall survival was extended by chemo-immunotherapy with VEGFi (19.0 versus 15.7 mo; HR: 0.77; 95% CI: 0.67-0.89; p = 0.00046) and without VEGFi (18.1 versus 15.7 mo; HR: 0.86; 95% CI: 0.76-0.97; p = 0.018) compared with chemotherapy with or without VEGFi. However, adding VEGFi to chemo-immunotherapy did not extend the median overall survival compared with chemo-immunotherapy alone (HR: 0.90; 95% CI: 0.77-1.05; p = 0.18). These results were consistent in trial-level HR meta-analyses, where chemo-immunotherapy, only when combined with VEGFi, also improved the objective response rate versus chemotherapy with or without VEGFi. Patients with PD-L1 more than or equal to 1% or L858R mutations achieved greater PFS benefit with chemo-immunotherapy with or without VEGFi. CONCLUSION: Chemo-immunotherapy with or without VEGFi may produce a modest survival improvement in select patients with EGFR-mutated NSCLC compared with chemotherapy. Identifying biomarkers able to predict a clinically meaningful benefit is warranted.