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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).
Cancer 2018; 124(19):3830-3838C

Abstract

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.

Authors+Show Affiliations

Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.Department of Thoracic Oncology, Toneyama National Hospital, National Hospital Organization, Toyonaka, Japan.Department of Thoracic Oncology, Toneyama National Hospital, National Hospital Organization, Toyonaka, Japan.Department of Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.Department of Medical Oncology, Takarazuka City Hospital, Takarazuka, Japan.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30192383

Citation

Hata, Akito, et al. "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)." Cancer, vol. 124, no. 19, 2018, pp. 3830-3838.
Hata A, Katakami N, Kaji R, et al. 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). Cancer. 2018;124(19):3830-3838.
Hata, A., Katakami, N., Kaji, R., Yokoyama, T., Kaneda, T., Tamiya, M., ... The Hanshin Oncology Group, F. (2018). 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). Cancer, 124(19), pp. 3830-3838. doi:10.1002/cncr.31678.
Hata A, et al. 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). Cancer. 2018 10 1;124(19):3830-3838. PubMed PMID: 30192383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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). AU - Hata,Akito, AU - Katakami,Nobuyuki, AU - Kaji,Reiko, AU - Yokoyama,Toshihide, AU - Kaneda,Toshihiko, AU - Tamiya,Motohiro, AU - Inoue,Takako, AU - Kimura,Hiromi, AU - Yano,Yukihiro, AU - Tamura,Daisuke, AU - Morita,Satoshi, AU - Negoro,Shunichi, AU - The Hanshin Oncology Group,For, Y1 - 2018/09/07/ PY - 2018/04/11/received PY - 2018/05/26/revised PY - 2018/06/01/accepted PY - 2018/9/8/pubmed PY - 2018/9/8/medline PY - 2018/9/8/entrez KW - T790M KW - acquired resistance KW - afatinib KW - bevacizumab KW - epidermal growth factor receptor (EGFR) mutation KW - non-small cell lung cancer SP - 3830 EP - 3838 JF - Cancer JO - Cancer VL - 124 IS - 19 N2 - 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. SN - 1097-0142 UR - https://www.unboundmedicine.com/medline/citation/30192383/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__ L2 - https://doi.org/10.1002/cncr.31678 DB - PRIME DP - Unbound Medicine ER -