EGFR EXON 19 DELETION OR L858R MUTATIONS….Progression on erlotinib (± ramucirumab or bevacizumab), afatinib, gefitinib, or dacomitinib….SUBSEQUENT THERAPY...Continue erlotinib (± ramucirumab or bevacizumab) or afatinib or gefitinib or dacomitinib (if T790M-).

Subgroup analysis demonstrated that in deletion within exon 19 (19del) mutation subgroup, the combination therapy could only prolong PFS (HR = 0.60, 95% CI 0.47-0.76; p < 0.0001)...and also in leucine-to-arginine substitution in exon 21 (L858R) mutation subgroup (HR = 0.59, p < 0.0001...).

First-generation EGFR-TKI with bevacizumab improved treatment efficacy in real-world patients of NSCLC with EGFR mutation. Patients with brain metastasis received additional OS benefit from this treatment....Patients who received a first-generation EGFR-TKI (gefitinib or erlotinib) monotherapy or with bevacizumab as the first-line treatment of advanced NSCLC with common EGFR mutation (exon 19 deletion or exon 21 L858R) were retrospectively included....Subgroup OS analysis indicated additional benefit of bevacizumab in patients with brain metastasis (HR 0.28 [95% CI 0.10–0.78]; p = 0.015), patients who had ECOG PS 0–1 (HR 0.38 [95% CI 0.17–0.86]; p = 0.020), patients with EGFR 19 deletion mutation (HR 0.33 [95% CI 0.11–0.98]; p = 0.046) and patients who had no liver metastasis (HR 0.26 [95% CI 0.10–0.66]; p = 0.005, Fig. 2).

Twenty-five patients were enrolled in this study, and the median age was 80 years. Fifteen (60.0%) and 10 patients (40.0%) had exon 21 L858R mutations and exon 19 deletions, respectively. The median progression-free survival from enrollment was 12.6 months [95% confidence interval (CI): 8.0-33.7 months]. The objective response rate was 88.0% [95% CI: 74.0%-99.0%], and the disease control rate was 100% [95% CI: 88.7%-100%].

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....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)....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.