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EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer.
Cancer Chemother Pharmacol 2015; 76(4):835-41CC

Abstract

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.

Authors+Show Affiliations

Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan. a-hata@fbri.org.Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26349474

Citation

Otsuka, Kyoko, et al. "EGFR-TKI Rechallenge With Bevacizumab in EGFR-mutant Non-small Cell Lung Cancer." Cancer Chemotherapy and Pharmacology, vol. 76, no. 4, 2015, pp. 835-41.
Otsuka K, Hata A, Takeshita J, et al. EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer. Cancer Chemother Pharmacol. 2015;76(4):835-41.
Otsuka, K., Hata, A., Takeshita, J., Okuda, C., Kaji, R., Masago, K., ... Katakami, N. (2015). EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer. Cancer Chemotherapy and Pharmacology, 76(4), pp. 835-41. doi:10.1007/s00280-015-2867-8.
Otsuka K, et al. EGFR-TKI Rechallenge With Bevacizumab in EGFR-mutant Non-small Cell Lung Cancer. Cancer Chemother Pharmacol. 2015;76(4):835-41. PubMed PMID: 26349474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer. AU - Otsuka,Kyoko, AU - Hata,Akito, AU - Takeshita,Jumpei, AU - Okuda,Chiyuki, AU - Kaji,Reiko, AU - Masago,Katsuhiro, AU - Fujita,Shiro, AU - Katakami,Nobuyuki, Y1 - 2015/09/08/ PY - 2015/07/25/received PY - 2015/09/02/accepted PY - 2015/9/10/entrez PY - 2015/9/10/pubmed PY - 2015/12/19/medline KW - Acquired resistance KW - Bevacizumab KW - EGFR mutation KW - EGFR-TKI rechallenge KW - T790M SP - 835 EP - 41 JF - Cancer chemotherapy and pharmacology JO - Cancer Chemother. Pharmacol. VL - 76 IS - 4 N2 - 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. SN - 1432-0843 UR - https://www.unboundmedicine.com/medline/citation/26349474/EGFR_TKI_rechallenge_with_bevacizumab_in_EGFR_mutant_non_small_cell_lung_cancer_ L2 - https://dx.doi.org/10.1007/s00280-015-2867-8 DB - PRIME DP - Unbound Medicine ER -