EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer

• Published in: Cancer chemotherapy and pharmacology 2015-10, Vol.76 (4), p.835-841
• Main Authors: Otsuka, Kyoko, Hata, Akito, Takeshita, Jumpei, Okuda, Chiyuki, Kaji, Reiko, Masago, Katsuhiro, Fujita, Shiro, Katakami, Nobuyuki
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Amino Acid Substitution; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab - administration & dosage; Bevacizumab - adverse effects; Bevacizumab - therapeutic use; Biopsy; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Drug Monitoring; Drug Resistance, Neoplasm; Erlotinib Hydrochloride - administration & dosage; Erlotinib Hydrochloride - adverse effects; Erlotinib Hydrochloride - therapeutic use; Female; Humans; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Oncology; Original Article; Pharmacology/Toxicology; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Retrospective Studies; Survival Analysis
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-015-2867-8

Background Efficacies 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. Methods We 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. Results Between 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. Conclusions EGFR-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.