• Akito Hata, Nobuyuki Katakami, Reiko Kaji, Toshihide Yokoyama, Toshihiko Kaneda, Motohiro Tamiya, Takako Inoue, Hiromi Kimura, Yukihiro Yano, Daisuke Tamura, Satoshi Morita, Shunichi Negoro, and For The Hanshin Oncology Group.
• Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
• Cancer. 2018 Oct 1; 124 (19): 3830-3838.

BackgroundPreclinical 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.MethodsPatients 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.ResultsBetween 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.ConclusionsAfatinib plus bevacizumab demonstrated clinical efficacy and safety after AR to EGFR TKIs and could be a therapeutic salvage option for T790M- populations.© 2018 American Cancer Society.

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