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

Takashi Ninomiya, Nobuhisa Ishikawa, Koji Inoue, Toshio Kubo, Masayuki Yasugi, Takuo Shibayama, Tadashi Maeda, Kazunori Fujitaka, Masahiro Kodani, Toshihide Yokoyama, Shoichi Kuyama, Nobuaki Ochi, Yutaka Ueda, Seigo Miyoshi, Toshiyuki Kozuki, Yoshihiro Amano, Tetsuya Kubota, Keisuke Sugimoto, Akihiro Bessho, Tomoya IshiiKazuhiko Watanabe, Isao Oze, Katsuyuki Hotta, Katsuyuki Kiura

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)134-138
Number of pages5
JournalClinical Lung Cancer
Volume20
Issue number2
DOIs
Publication statusPublished - Mar 2019

Keywords

  • Anti-angiogenesis
  • EGFR-TKI
  • Molecular targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Ninomiya, T., Ishikawa, N., Inoue, K., Kubo, T., Yasugi, M., Shibayama, T., Maeda, T., Fujitaka, K., Kodani, M., Yokoyama, T., Kuyama, S., Ochi, N., Ueda, Y., Miyoshi, S., Kozuki, T., Amano, Y., Kubota, T., Sugimoto, K., Bessho, A., ... 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), 134-138. https://doi.org/10.1016/j.cllc.2018.10.008