Response to crizotinib in advanced ALK-rearranged non-small cell lung cancers with different ALK-fusion variants

Yan Li, Tongtong Zhang, Jing Zhang, Wenbin Li, Pei Yuan, Puyuan Xing, Zhou Zhang, Shannon Chuai, Junling Li, Jianming Ying*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Introduction: Anaplastic lymphoma kinase (ALK) rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). NSCLCs with ALK-rearrangement can be effectively treated with crizotinib. However, magnitude and duration of responses are found to be heterogeneous. This study explored the clinical efficacy of crizotinib in different ALK variants. Methods: Among 96 ALK-rearrangement patients treated with crizotinib, 60 patients were identified with tumor specimens that could be evaluated by next-generation sequencing (NGS). We retrospectively evaluated the efficacy of crizotinib in different ALK variants. Results: The median Progression-free survival (PFS) of the 96 ALK-rearrangement patients was 14.17 months. Among the 60 patients with NGS results, the most frequent variants were variant 3a/b (33.33%), variant 1 (23.33%) and variant 2 (15.00%). The percentage of rare EML4-ALK variants and non EML4-ALK variants were 10.00% and 18.33%. Survival analysis showed that patients with variant 2 appeared to have longer PFS than others (P =.021); also, patients with TP53 mutation seemed to have an unfavorable PFS than those with TP53 wild-type with a borderline p value (P =.068). After adjusting for other baseline characteristics, EML4-ALK variant 2 was identified as an important factor for a better PFS of crizotinib. We also found that patients with variant 3a/b had shorter duration of response to crizotinib; however, no significant difference of PFS was observed between the PFS of variant3a/b and non-v3 EML4-ALK variants. Conclusions: Our results indicate prolonged PFS in patients with EML4-ALK variant 2.

Original languageEnglish (US)
Pages (from-to)128-133
Number of pages6
JournalLung Cancer
Volume118
DOIs
StatePublished - Apr 2018
Externally publishedYes

Keywords

  • ALK translocation
  • Crizotinib
  • Next-generation sequencing
  • Non-small cell lung cancer
  • Variants

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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