Lorlatinib for advanced ROS1+ non-small-cell lung cancer: results of the IFCT-1803 LORLATU study

ESMO Open. 2022 Apr;7(2):100418. doi: 10.1016/j.esmoop.2022.100418. Epub 2022 Feb 26.


Introduction: ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) is a rare lung cancer with limited treatment options. Phase I-II studies with ROS1-tyrosine kinase inhibitors (TKIs) included small numbers of patients and real-world data are lacking. We investigate the efficacy and safety of lorlatinib, a third-generation TKI targeting ALK and ROS1, in patients with ROS1+ NSCLC treated through an expanded access program.

Methods: Consecutive patients with advanced ROS1+ NSCLC treated with lorlatinib between October 2015 and June 2019 were included. Data were collected from medical records. The primary endpoint was progression-free survival.

Results: Out of the 80 patients included, 47(59%) were female, 49(62%) never smokers (less than 100 cigarettes over the lifetime), and 68(85%) had stage IV NSCLC at diagnosis. Most frequent histology was adenocarcinoma (95%) and median age was 58.2 years. At the time of lorlatinib initiation, 51(64%) patients had brain metastases and 55(81%) were PS 0-1. Lorlatinib was administered as second/third/fourth/fifth+ line in 29%/28%/18%/26% of patients. All patients previously received at least one ROS1 TKI, and 55(69%) previously received chemotherapy. Median follow-up from lorlatinib initiation was 22.2 months. Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months [95% confidence interval (CI) 5.0-9.9 months] and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%. Treatment was stopped due to toxicity in 10 patients (13%). The safety profile was consistent with previously published data.

Conclusions: Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.

Keywords: NSCLC; ROS1; brain metastases; chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Female
  • Humans
  • Lactams
  • Lactams, Macrocyclic / pharmacology
  • Lactams, Macrocyclic / therapeutic use
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Protein-Tyrosine Kinases / therapeutic use
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / therapeutic use
  • Pyrazoles


  • Aminopyridines
  • Lactams
  • Lactams, Macrocyclic
  • Proto-Oncogene Proteins
  • Pyrazoles
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • lorlatinib