• Kyoko Otsuka, Akito Hata, Jumpei Takeshita, Chiyuki Okuda, Reiko Kaji, Katsuhiro Masago, Shiro Fujita, and Nobuyuki Katakami.
• Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
• Cancer Chemother. Pharmacol. 2015 Oct 1; 76 (4): 835-41.

BackgroundEfficacies of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) rechallenge have been demonstrated in EGFR-mutant non-small cell lung cancer (NSCLC). However, their efficacies were only moderate. Some preclinical studies suggested synergistic effects of bevacizumab to EGFR-TKI in TKI-resistant models.MethodsWe retrospectively evaluated clinical efficacy and safety of EGFR-TKI rechallenge with bevacizumab. Rebiopsy was performed on all studied cases to examine T790M-resistant mutation status.ResultsBetween January 2010 and June 2014, a total of 24 EGFR-mutant NSCLC patients who had been previously treated with EGFR-TKIs (gefitinib, erlotinib, and/or afatinib) received EGFR-TKI rechallenge with bevacizumab. Twenty-two (92 %) patients underwent erlotinib and two (8 %) gefitinib as rechallenge EGFR-TKIs in combination with bevacizumab. Three patients achieved partial response, and 18 had stable disease, resulting in the response rate (RR) of 13 % and disease control rate (DCR) of 88 %, respectively. The median progression-free survival (PFS) was 4.1 [95 % confidence interval (CI) 2.3-4.9] months, and the median overall survival (OS) was 13.5 (95 % CI 9.7-27.4) months. The RR, DCR, median PFS, and median OS for T790M-positive versus T790M-negative were 0 versus 18 % (p = 0.530), 86 versus 88 % (p = 1.00), 3.3 versus 4.1 months (p = 0.048), and 15.1 versus 13.5 months (p = 0.996), respectively. Severe adverse events (≥grade 3): grade 3 of 1 (4 %) rash; grade 3 of 1 (4 %) paronychia; grade 3 of 1 (4 %) hypertension; and grade 3 of 1 (4 %) anemia, were observed.ConclusionsEGFR-TKI rechallenge with bevacizumab demonstrated higher DCR and modestly longer PFS than historical data on EGFR-TKI rechallenge alone. Its activity was notably higher in T790M-negative population.

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