학술논문
Phase II Trial of the Combination of Alectinib with Bevacizumab in Alectinib Refractory ALK-Positive Nonsquamous Non-Small-Cell Lung Cancer (NLCTG1501)
Document Type
article
Author
Satoshi Watanabe; Kazuko Sakai; Naoya Matsumoto; Jun Koshio; Akira Ishida; Tetsuya Abe; Daisuke Ishikawa; Tomohiro Tanaka; Ami Aoki; Tomosue Kajiwara; Kenichi Koyama; Satoru Miura; Yuka Goto; Tomoki Sekiya; Ryo Suzuki; Kohei Kushiro; Toshiya Fujisaki; Naohiro Yanagimura; Aya Ohtsubo; Satoshi Shoji; Koichiro Nozaki; Yu Saida; Hirohisa Yoshizawa; Kazuto Nishio; Toshiaki Kikuchi
Source
Cancers, Vol 15, Iss 1, p 204 (2022)
Subject
Language
English
ISSN
2072-6694
Abstract
Anaplastic lymphoma kinase (ALK)-positive lung cancer is a rare cancer that occurs in approximately 5% of non-small-cell lung cancer (NSCLCs) patients. Despite the excellent efficacy of ALK-tyrosine kinase inhibitor in ALK-positive NSCLCs, most patients experience resistance. We conducted a phase II study to investigate the combination of alectinib with bevacizumab in ALK-positive NSCLC patients after failure of alectinib. In this study, ALK-positive nonsquamous NSCLC patients previously treated with alectinib received bevacizumab 15 mg/kg on day 1 every 3 weeks and alectinib 600 mg/day until disease progression. The primary endpoints were progression-free survival (PFS) and the safety of alectinib and bevacizumab. The secondary endpoints included overall survival (OS) and correlation of circulating tumor DNA and plasma proteins with PFS. Of the 12 patients treated, the median PFS was 3.1 months (95% CI 1.2–16.1), and the median OS was 24.1 months (95% CI 8.3-not estimable). The EML4-ALK fusion gene in circulating tumor DNA was significantly correlated with shorter PFS (1.2 months vs. 11.4 months, HR 5.2, p = 0.0153). Two patients experienced grade 3 adverse events; however, none of the patients required dose reduction. Although the primary endpoint was not met, alectinib combined with bevacizumab showed clinical efficacy in ALK-positive patients.