The epidermal growth factor receptor gene (EGFR) plays a major role in metastatic non-small cell lung cancer (NSCLC) and presents as a therapeutic target. It has been previously shown in patients with an EGFR mutation that EGFR tyrosine kinase inhibitors lead to benefits on progression-free survival (PFS).1,2 Unfortunately, patients may acquire resistance to these kinase inhibitors, resulting in disease progression, highlighting the need for novel therapy options.3 The FL-ALTER phase III study investigated the potential of the EGFR tyrosine kinase inhibitor gefitinib in combination with anlotinib, a multikinase inhibitor, in patients with untreated EGFR-mutated NSCLC.4
Methods
315 Patients aged above 18 years with histologically-confirmed stage IIIB or IV NSCLC were enrolled. Patients with an ex19del or ex21L858R EGFR mutation were eligible. No prior chemotherapy or targeted therapy were permitted. Patients were randomised 1:1 to receive gefitinib (250mg) plus anlotinib (12mg) or gefitinib plus placebo orally on days 1-14 per cycle (2 weeks on, 1 week off).
Results
At the prespecified final analysis, an improvement in PFS for the gefitinib + anlotinib arm vs. gefitinib + placebo was reported (median PFS: 14.8 months vs. 11.2 months, HR[95% CI]: 0.64 [0.48-0.8], p=0.003). More specifically, patients with brain metastases and those with EGFR amplification of high tumour mutation load benefited more (median PFS, brain metastases: 13.8 months vs. 8.3 months; ex19del: 15.2 months vs. 12.2 months; ex21L858R: 12.9 months vs. 8.6 months). Grade ≥3 treatment-emergent adverse events occurred in 49.7% of patients in the gefitinib + anlotinib arm vs. 31% in the gefitinib + placebo arm.
Conclusion
Anlotinib + gefitinib significantly improved PFS in patients with treatment-naïve NSCLC with EGFR mutation and presented a manageable safety profile.
References
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