Crizotinib in Chinese Patients with ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice

Target Oncol. 2019 Jun;14(3):315-323. doi: 10.1007/s11523-019-00636-6.

Abstract

Background: Approximately 1-2% of patients with non‒small-cell lung cancer (NSCLC) harbor ROS1 rearrangements. Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC.

Objective: Our objective was to analyze the efficacy and safety of crizotinib treatment in Chinese patients with advanced NSCLC with ROS1 rearrangement in real-world clinical practice.

Methods: We included 35 patients with ROS1-positive NSCLC in this retrospective analysis. All received crizotinib 250 mg twice daily between March 2016 and April 2018 at the Fudan University Shanghai Cancer Center. All had histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangements, which were identified by fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, or next-generation sequencing. The main outcome measures were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events.

Results: The median age of the patients was 51.0 years; 23 (65.7%) were female and 28 (80.0%) were never smokers. All were diagnosed as having adenocarcinoma; eight patients (22.9%) had brain metastases at baseline. The ORR and DCR were 71.4% and 94.3%, respectively. The estimated median PFS was 11.0 months (95% confidence interval [CI] 7.8-14.2). The estimated median OS was 41.0 months (95% CI 22.5-59.5). Elevated transaminases (54.3%), vision disorder (25.7%), elevated blood creatinine (22.9%), diarrhea (20.0%), and vomiting (20.0%) were the most commonly reported adverse effects.

Conclusion: Crizotinib was effective and well tolerated in Chinese patients with ROS1-positive advanced NSCLC in real-world clinical practice. The progression sites and patterns, as well as treatments after first disease progression on crizotinib were diverse. Crizotinib beyond progressive disease and local therapy after failure of crizotinib treatment were feasible and effective in clinical practice.

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Asian People / genetics*
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Crizotinib / therapeutic use*
  • Female
  • Follow-Up Studies
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Retrospective Studies
  • Salvage Therapy*
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Crizotinib
  • Protein-Tyrosine Kinases
  • ROS1 protein, human