Clinical treatment patterns, molecular characteristics and survival outcomes of ROS1-rearranged non-small cell lung cancer: A large multicenter retrospective study

Lung Cancer. 2024 Jun:192:107827. doi: 10.1016/j.lungcan.2024.107827. Epub 2024 May 21.

Abstract

Background: Non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements is a molecular subset that exhibits favorable responses to tyrosine kinase inhibitor (TKI) treatment than chemotherapy. This study investigated real-world treatment patterns and survival outcomes among patients with ROS1-rearranged advanced NSCLC.

Methods: We conducted a retrospective analysis of patients with ROS1-rearranged advanced NSCLC treated in four different hospitals in China from August 2018 to March 2022. The study analyzed gene fusion distribution, resistance patterns, and survival outcomes.

Results: ROS1 rearrangement occurs in 1.8 % (550/31,225) of our study cohort. CD74 was the most common ROS1 fusion partner, accounting for 45.8 %. Crizotinib was used in 73.9 % of patients in the first-line treatment, and an increased use of chemotherapy, ceritinib, and lorlatinib was seen in the second-line setting. Lung (43.2 %) and brain (27.6 %) were the most common sites of progression in first-line setting, while brain progression (39.2 %) was the most common site of progression in second-line. Median overall survival was 46 months (95 % confidence intervals: 39.6-52.4). First-line crizotinib use yielded significantly superior survival outcomes over chemotherapy in terms of progression-free (18.5 vs. 6.0; p < 0.001) and overall survival (49.8 vs. 37; p = 0.024). The choice of treatment in the latter line also had survival implications, wherein survival outcomes were better when first-line crizotinib was followed by sequential TKI therapy than first-line chemotherapy followed by TKI therapy.

Conclusions: Our study provided insights into the real-world treatment, drug resistance patterns, and survival outcomes among patients with ROS1-rearranged NSCLC. This information serves as a valuable reference for guiding the treatment of this molecular subset of NSCLC.

Keywords: Fusion partner; NSCLC; ROS1 rearrangement; Resistance; Survival.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminopyridines
  • Antigens, Differentiation, B-Lymphocyte
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • China / epidemiology
  • Crizotinib* / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Rearrangement*
  • Histocompatibility Antigens Class II
  • Humans
  • Lactams
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases* / genetics
  • Proto-Oncogene Proteins* / genetics
  • Pyrazoles / therapeutic use
  • Retrospective Studies
  • Survival Rate

Substances

  • ROS1 protein, human
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Crizotinib
  • Protein Kinase Inhibitors
  • invariant chain
  • Pyrazoles
  • lorlatinib
  • Aminopyridines
  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Lactams