Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR‐mutant non–small cell lung cancer: Multicenter, single‐arm, phase 2 trial (ABC Study)

BACKGROUND Preclinical studies suggested that the addition of bevacizumab could overcome acquired resistance (AR) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the clinical efficacy and safety of a combination of afatinib and bevacizumab after AR. METHODS Patients with EGFR‐mutant non–small cell lung cancer after AR were enrolled during any line of therapy. Afatinib was prescribed at 30 mg, and 15 mg/kg bevacizumab was administered every 3 weeks until progression. RESULTS Between October 2014 and May 2017, 32 eligible patients were evaluated. The mutation subtypes were Del‐19 (20 [63%]), L858R (11 [34%]), and L861Q (1 [3%]). T790M was detected in 14 patients (44%). The median number of prior regimens was 4 (range, 1‐10). Six patients obtained a partial response, and 23 had stable disease; this resulted in an objective response rate (ORR) of 18.8% (95% confidence interval [CI], 7.2%‐36.4%) and a disease control rate of 90.7% (95% CI, 75.0%‐98.0%). The median progression‐free survival (PFS) was 6.3 months (95% CI, 3.9‐8.7 months). The ORRs and median PFS times of T790M+ and T790M− patients were 14.3% and 22.2%, respectively, and 6.3 and 7.1 months, respectively; those of Del‐19 and L858R patients were 20.0% and 11.1%, respectively, and 6.3 and 5.1 months, respectively. Grade 3 or higher adverse events (incidence ≥ 10%) included paronychia (25%), hypertension (41%), and proteinuria (19%). There were no treatment‐related deaths, interstitial lung disease, or bevacizumab‐associated severe bleeding. CONCLUSIONS Afatinib plus bevacizumab demonstrated clinical efficacy and safety after AR to EGFR TKIs and could be a therapeutic salvage option for T790M− populations. Preclinical studies have encouraged the clinical investigation of a combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and bevacizumab after acquired resistance to EGFR tyrosine kinase inhibitors. In this phase 2 study, afatinib‐bevacizumab combination therapy shows clinical efficacy and safety as well as potency for T790M populations.