Abstract
Purpose
Erlotinib is indicated as first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor–receptor (EGFR) mutation. Addition of a vascular endothelial growth factor (VEGF) inhibitor (anti-VEGF) in combination with the tyrosine-kinase inhibitor erlotinib in this setting is controversial.
Methods
We conducted a meta-analysis of randomized trials comparing anti-VEGF plus erlotinib vs erlotinib alone as first-line therapy for advanced NSCLC harboring an EGFR mutation. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and median duration of response (DOR). A fixed-effect model was used.
Results
Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al.), and another evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients, 654 (53.2%) with exon 19 deletion (ex19del) and 568 (46.8%) with EGFRL858R. Patients were predominantly women (63%), Asians (85%) and non-smokers (60%); the median age was 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with prolonged PFS (hazards ratio [HR] 0.59 [95% confidence interval (CI) 0.51–0.69]; p < 0.00001). The combination achieved significantly longer median DOR (p < 0.005). Based on interim analyses, OS (HR 0.90 [0.68–1.19]; p = 0.45) and ORR (odds ratio 1.19 [95% CI 0.91–1.55]; p = 0.21 were comparable.
Conclusions
For patients with untreated, advanced, EGFR-mutation–harboring NSCLCs, the anti-VEGF + erlotinib combination, compared to erlotinib alone, was associated with significantly prolonged PFS but mature data for OS are needed to confirm the benefit of this strategy.
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JBA was supported by grants from Fondation pour la Recherche Médicale (FRM). CC reports consultancy fees from Astra Zeneca, Boehringer Ingelheim, MSD, Pierre Fabre Oncology, Lilly, Roche, Bristol- Myers Squibb, Novartis, Lilly, Pierre Fabre Oncology and Boehringer Ingelheim.
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Landre, T., Des Guetz, G., Chouahnia, K. et al. First-line angiogenesis inhibitor plus erlotinib versus erlotinib alone for advanced non-small-cell lung cancer harboring an EGFR mutation. J Cancer Res Clin Oncol 146, 3333–3339 (2020). https://doi.org/10.1007/s00432-020-03311-w
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DOI: https://doi.org/10.1007/s00432-020-03311-w