Crizotinib in ROS1-rearranged non-small-cell lung cancer

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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Author(s)

  • Alice T. Shaw
  • Sai-Hong I. Ou
  • Yung-Jue Bang
  • D. Ross Camidge
  • Benjamin J. Solomon
  • Ravi Salgia
  • Gregory J. Riely
  • Marileila Varella-Garcia
  • Geoffrey I. Shapiro
  • Daniel B. Costa
  • Robert C. Doebele
  • Long Phi Le
  • Weiwei Tan
  • Patricia Stephenson
  • S. Martin Shreeve
  • Lesley M. Tye
  • James G. Christensen
  • Keith D. Wilner
  • Jeffrey W. Clark
  • A. John Iafrate

Detail(s)

Original languageEnglish
Pages (from-to)1963-1971
Journal / PublicationNew England Journal of Medicine
Volume371
Issue number21
Publication statusPublished - 20 Nov 2014
Externally publishedYes

Abstract

Background: Chromosomal rearrangements of the gene encoding ROS1 proto-oncogene receptor tyrosine kinase (ROS1) define a distinct molecular subgroup of non-small-cell lung cancers (NSCLCs) that may be susceptible to therapeutic ROS1 kinase inhibition. Crizotinib is a small-molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and another proto-oncogene receptor tyrosine kinase, MET. Methods: We enrolled 50 patients with advanced NSCLC who tested positive for ROS1 rearrangement in an expansion cohort of the phase 1 study of crizotinib. Patients were treated with crizotinib at the standard oral dose of 250 mg twice daily and assessed for safety, pharmacokinetics, and response to therapy. ROS1 fusion partners were identified with the use of next-generation sequencing or reverse-transcriptase-polymerase-chain-reaction assays. Results: The objective response rate was 72% (95% confidence interval [CI], 58 to 84), with 3 complete responses and 33 partial responses. The median duration of response was 17.6 months (95% CI, 14.5 to not reached). Median progression-free survival was 19.2 months (95% CI, 14.4 to not reached), with 25 patients (50%) still in follow-up for progression. Among 30 tumors that were tested, we identified 7 ROS1 fusion partners: 5 known and 2 novel partner genes. No correlation was observed between the type of ROS1 rearrangement and the clinical response to crizotinib. The safety profile of crizotinib was similar to that seen in patients with ALK-rearranged NSCLC. Conclusions: In this study, crizotinib showed marked antitumor activity in patients with advanced ROS1-rearranged NSCLC. ROS1 rearrangement defines a second molecular subgroup of NSCLC for which crizotinib is highly active.

Citation Format(s)

Crizotinib in ROS1-rearranged non-small-cell lung cancer. / Shaw, Alice T.; Ou, Sai-Hong I.; Bang, Yung-Jue; Camidge, D. Ross; Solomon, Benjamin J.; Salgia, Ravi; Riely, Gregory J.; Varella-Garcia, Marileila; Shapiro, Geoffrey I.; Costa, Daniel B.; Doebele, Robert C.; Le, Long Phi; Zheng, Zongli; Tan, Weiwei; Stephenson, Patricia; Shreeve, S. Martin; Tye, Lesley M.; Christensen, James G.; Wilner, Keith D.; Clark, Jeffrey W.; Iafrate, A. John.

In: New England Journal of Medicine, Vol. 371, No. 21, 20.11.2014, p. 1963-1971.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review