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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
05:17

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

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Crizotinib presented with promising efficacy but for concomitant mutation in next-generation sequencing-identified

Liang Zeng1, Yizhi Li1, Lili Xiao1

  • 1Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, China, zhangyongchang@csu.edu.cn; yangnong0217@163.com.

Oncotargets and Therapy
|November 10, 2018
PubMed
Abstract

Insights

Crizotinib shows high efficacy in ROS1-rearranged non-small-cell lung cancer (NSCLC) patients identified by next-generation sequencing (NGS). Concomitant mutations may negatively impact progression-free survival in these patients.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Next-generation sequencing (NGS) has identified ROS1 rearrangements in non-small-cell lung cancer (NSCLC).
  • Real-world data on tyrosine kinase inhibitor (TKI) treatment outcomes for ROS1-rearranged NSCLC are limited.
  • Evaluating crizotinib's efficacy and influencing factors in a real-world setting is crucial.

Purpose of the Study:

  • To assess the efficacy and safety of crizotinib in patients with ROS1-rearranged NSCLC identified through NGS.
  • To identify factors influencing treatment outcomes, including concomitant mutations and fusion variants.

Main Methods:

  • Retrospective analysis of 1,466 NSCLC patients undergoing targeted NGS.
  • Identification of 22 patients with ROS1 rearrangement.
  • Evaluation of crizotinib efficacy, safety, and subgroup analyses (concomitant mutations, brain metastasis, fusion variants).

Main Results:

  • ROS1 rearrangement occurred in 1.5% of NSCLC patients.
  • CD74 was the most common fusion partner (50%).
  • Concomitant mutations were detected in 23% of patients.
  • Crizotinib demonstrated an 89% overall response rate (ORR) and a 13.6-month median progression-free survival (mPFS).
  • Patients with exclusive ROS1 rearrangement had significantly longer PFS than those with concomitant mutations (15.5 vs. 8.5 months, P=0.0213).
  • No new safety concerns were identified.

Conclusions:

  • Crizotinib is highly effective for ROS1-rearranged advanced NSCLC in real-world practice.
  • Findings align with previous clinical trials using FISH/real-time PCR for ROS1 diagnosis.
  • Concomitant mutations are potentially common and may reduce crizotinib's PFS benefit in ROS1-rearranged NSCLC.
Keywords:
NSCLCROS1TP53concomitant mutationcrizotinibefficacynext-generation sequencingsafety

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