Bevacizumab Plus Erlotinib in Chinese Patients with Untreated, EGFR -Mutated, Advanced NSCLC (ARTEMIS-CTONG1509): A Multicenter Phase 3 Study

Most patients with advanced non-small-cell lung cancer (NSCLC) develop resistance to first-line treatment. However, dual epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathway inhibition may delay therapeutic resistance. We assessed erlotinib plus bevacizumab versus erlotinib alone in an open-label, phase 3 study of Chinese patients with untreated EGFR-mutated metastatic NSCLC. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). Safety was assessed in all treated patients. In total, 311 patients received bevacizumab plus erlotinib (n=157) or erlotinib only (n=154). Median IRC-assessed PFS was 17.9 months (95% confidence interval [CI] 15.2–19.9) for bevacizumab plus erlotinib and 11.2 months (95% CI 9.7–13.8) for erlotinib only (Hazard Ratio 0.55 [95% CI 0.41–0.73], p < 0.001). Grade ≥3 treatment-related adverse events occurred in 86 (54.8%) and 40 (26.1%) patients, respectively. Bevacizumab plus erlotinib significantly improved PFS in patients with untreated EGFR-mutated NSCLC. The baseline mutation landscape was comparable between the two groups with 41% of patients in bevacizumab plus erlotinib group and 45% of patients in erlotinib group harboring concurrent mutations including amplification, oncogenic frusions, MAPK/PI3K alterations and cell cycle gene alterations. The addition of bevacizumab[WT1]  did not alter the molecular dynamics of mutations during the course of treatment. At disease progression, EGFR T790M was the major resistance mechanism, acquired by 40% of patients in bevacizumab plus erlotinib group and 61% of patients in erlotinib only group, with a comprable detection rate in both groups (p=0.188).