Sequential therapy of crizotinib followed by alectinib for non-small cell lung cancer harbouring anaplastic lymphoma kinase rearrangement (WJOG9516L): A multicenter retrospective cohort study

Kentaro Ito, Takeharu Yamanaka, Hidetoshi Hayashi, Yoshihiro Hattori, Kazumi Nishino, Haruki Kobayashi, Yuko Oya, Toshihide Yokoyama, Takashi Seto, Koichi Azuma, Tomoya Fukui, Toshiyuki Kozuki, Atsushi Nakamura, Kentaro Tanaka, Katsuya Hirano, Takashi Yokoi, Haruko Daga, Shinya Sakata, Daichi Fujimoto, Masahide MoriKen Maeno, Takuya Aoki, Atsuhisa Tamura, Satoru Miura, Satoshi Watanabe, Hiroaki Akamatsu, Osamu Hataji, Kensuke Suzuki, Shigeto Hontsu, Koji Azuma, Akihiro Bessho, Akihito Kubo, Motoyasu Okuno, Kazuhiko Nakagawa, Nobuyuki Yamamoto

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited. Methods: We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the ‘TTF of CRZ’ plus the ‘TTF of ALEC’ if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group. Results: Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio [HR], 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001). Conclusion: The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.

Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalEuropean Journal of Cancer
Volume145
DOIs
Publication statusPublished - Mar 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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