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Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol.
Clin Lung Cancer 2019; 20(2):134-138CL

Abstract

Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has demonstrated a significant survival benefit over platinum-based chemotherapy in a first-line setting in advanced non-small-cell lung cancer (NSCLC) harboring EGFR exon 19 deletion. In addition, we and other groups have shown there to be favorable progression-free survival (PFS) outcomes, with acceptable toxicity profiles, with bevacizumab and first-generation EGFR-TKI combination therapy. On the basis of the above, we hypothesized that a combination of bevacizumab and afatinib could potentially improve efficacy. In our phase 1 study, a daily 30 mg dose of afatinib and 15 mg/kg intravenous bevacizumab every 3 weeks was well tolerated and was defined as the recommended dose. We have initiated a randomized phase 2 trial comparing afatinib (30 mg daily) and bevacizumab (15 mg/kg every 3 weeks) with afatinib (40 mg daily) alone for nonsquamous NSCLC harboring EGFR common mutations as a first-line therapy. A total of 100 patients will be enrolled onto this study and randomized in a 1:1 ratio. Patients will continue to receive treatment until disease progression or unacceptable toxicity. The primary end point is PFS, and the secondary end points are overall survival, tumor response, and time to treatment failure. The power is greater than 50% under the assumptions of a median PFS of 12 months for the afatinib group and a hazard ratio of 0.6 for the combination group (2-sided α = 0.05). We hypothesize that the combination therapy will be more efficacious than standard therapies for EGFR-mutant NSCLC patients.

Authors+Show Affiliations

Health Service Center, Okayama University, Okayama, Japan; Department of Respiratory Medicine and Allergy, Okayama University Hospital, Okayama, Japan. Electronic address: tninomiya5@okayama-u.ac.jp.Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan.Department of Respiratory Medicine, Ehime Prefectural Central Hospital, Matsuyama, Japan.Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.Department of Respiratory, Chugoku Central Hospital, Fukuyama, Japan.Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan.Department of Medical Oncology, National Hospital Organization, Yamaguchi-Ube Medical Center, Ube, Japan.Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Japan.Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.Department of Respiratory Medicine, Iwakuni Clinical Center, Iwakuni, Japan.Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.Department of Respiratory Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Japan.Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Japan.Department of Thoracic Oncology and Medicine, National Hospital Organization, Shikoku Cancer Center, Matsuyama, Japan.Department of Internal Medicine Division of Medical Oncology & Respiratory Medicine Shimane University Faculty of Medicine, Izumo, Japan.Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nangoku, Japan.Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital, Kobe, Japan.Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan.Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan.Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.Department of Respiratory Medicine and Allergy, Okayama University Hospital, Okayama, Japan.

Pub Type(s)

Clinical Trial Protocol
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30514667

Citation

Ninomiya, Takashi, et al. "Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol." Clinical Lung Cancer, vol. 20, no. 2, 2019, pp. 134-138.
Ninomiya T, Ishikawa N, Inoue K, et al. Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol. Clin Lung Cancer. 2019;20(2):134-138.
Ninomiya, T., Ishikawa, N., Inoue, K., Kubo, T., Yasugi, M., Shibayama, T., ... Kiura, K. (2019). Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol. Clinical Lung Cancer, 20(2), pp. 134-138. doi:10.1016/j.cllc.2018.10.008.
Ninomiya T, et al. Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol. Clin Lung Cancer. 2019;20(2):134-138. PubMed PMID: 30514667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol. AU - Ninomiya,Takashi, AU - Ishikawa,Nobuhisa, AU - Inoue,Koji, AU - Kubo,Toshio, AU - Yasugi,Masayuki, AU - Shibayama,Takuo, AU - Maeda,Tadashi, AU - Fujitaka,Kazunori, AU - Kodani,Masahiro, AU - Yokoyama,Toshihide, AU - Kuyama,Shoichi, AU - Ochi,Nobuaki, AU - Ueda,Yutaka, AU - Miyoshi,Seigo, AU - Kozuki,Toshiyuki, AU - Amano,Yoshihiro, AU - Kubota,Tetsuya, AU - Sugimoto,Keisuke, AU - Bessho,Akihiro, AU - Ishii,Tomoya, AU - Watanabe,Kazuhiko, AU - Oze,Isao, AU - Hotta,Katsuyuki, AU - Kiura,Katsuyuki, Y1 - 2018/11/01/ PY - 2018/08/16/received PY - 2018/10/23/accepted PY - 2018/12/6/pubmed PY - 2018/12/6/medline PY - 2018/12/6/entrez KW - Anti-angiogenesis KW - EGFR-TKI KW - Molecular targeted therapy SP - 134 EP - 138 JF - Clinical lung cancer JO - Clin Lung Cancer VL - 20 IS - 2 N2 - Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has demonstrated a significant survival benefit over platinum-based chemotherapy in a first-line setting in advanced non-small-cell lung cancer (NSCLC) harboring EGFR exon 19 deletion. In addition, we and other groups have shown there to be favorable progression-free survival (PFS) outcomes, with acceptable toxicity profiles, with bevacizumab and first-generation EGFR-TKI combination therapy. On the basis of the above, we hypothesized that a combination of bevacizumab and afatinib could potentially improve efficacy. In our phase 1 study, a daily 30 mg dose of afatinib and 15 mg/kg intravenous bevacizumab every 3 weeks was well tolerated and was defined as the recommended dose. We have initiated a randomized phase 2 trial comparing afatinib (30 mg daily) and bevacizumab (15 mg/kg every 3 weeks) with afatinib (40 mg daily) alone for nonsquamous NSCLC harboring EGFR common mutations as a first-line therapy. A total of 100 patients will be enrolled onto this study and randomized in a 1:1 ratio. Patients will continue to receive treatment until disease progression or unacceptable toxicity. The primary end point is PFS, and the secondary end points are overall survival, tumor response, and time to treatment failure. The power is greater than 50% under the assumptions of a median PFS of 12 months for the afatinib group and a hazard ratio of 0.6 for the combination group (2-sided α = 0.05). We hypothesize that the combination therapy will be more efficacious than standard therapies for EGFR-mutant NSCLC patients. SN - 1938-0690 UR - https://www.unboundmedicine.com/medline/citation/30514667/Phase_2_Study_of_Afatinib_Alone_or_Combined_With_Bevacizumab_in_Chemonaive_Patients_With_Advanced_Non_Small_Cell_Lung_Cancer_Harboring_EGFR_Mutations:_AfaBev_CS_Study_Protocol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-7304(18)30292-4 DB - PRIME DP - Unbound Medicine ER -