Angiogenesis inhibitor plus erlotinib versus erlotinib alone as first-line for advanced non-small cell lung-cancer harboring EGFR mutation.

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9569 Background: Erlotinib is indicated in first line treatment for patients with Non-Small-Cell-Lung cancer (NSCLC) harbouring EGFR mutation. Addition of anti-VEGF in combination with erlotinib in this setting is controversial. Methods: We performed a meta-analysis of randomized trials comparing VEGF inhibitor plus erlotinib with erlotinib alone in first line treatment for advanced NSCLC harbouring EGFR mutation. The 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 one study evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients (654 with Ex19del and 568 with Leu858Arg);. Most of the patients were women (63%), Asian (85%) and non-smokers (60%), with a median age of 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with improvement of PFS (hazards ratio [HR]: 0.59, 95%CI: 0.51-0.69, p < 0.00001). Improvement in PFS was seen across all subgroups analyzed. Interim analysis of OS (HR: 0.90, 95%CI; 0.68-1.19, p = 0.45) and ORR (odds ratio [OR], 1.19, 0.91-1.55, p = 0.21) were not statistically significant. DOR was statistically longer with combination (p < 0.005). Conclusions: For patients with untreated advanced NSCLC with EGFR mutation, the anti-VEGF combination with erlotinib, compared with erlotinib alone, is associated with significantly improved PFS and DOR, but mature data for OS are needed to confirm the benefit of this strategy.

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