Real-world treatment patterns and survival of patients with ROS1 rearranged stage IV non-squamous NSCLC in the Netherlands

Introduction: Rearrangement of c-ros oncogene 1 (ROS1) is a rare gene alteration in patients with stage IV non-squamous non-small cell lung cancer (NSCLC). Molecular testing for ROS1 is recommended to enable primary treatment with tyrosine kinase inhibitors (TKI). Aim of this study was to describe real-world treatment patterns and survival for patients with ROS1 in the Netherlands.Methods: All non-squamous NSCLC stage IV patients, diagnosed 2015-2019, were identified from the population -based Netherlands Cancer Registry (N =19,871). For patients with ROS1 rearrangements (ROS1+ ) who received first line TKI, additional information about progression and second-line treatment was retrieved by active follow-up. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimators.Results: A total of 67 patients (0.43%) were diagnosed with a ROS1+ NSCLC. Systemic treatment was admin-istered in 75% which was most often TKI (n = 34) followed by chemotherapy (n = 14). Two-year OS for patients receiving upfront TKI versus other systemic treatment was 53% (95% CI 35-68) and 50% (95% CI 25-71), respectively. For patients receiving TKI, median OS was 24.3 months. Survival was inferior in case of brain metastasis (BM) at diagnosis (5.2 months). One in five patients receiving TKI as a first line treatment had BM at diagnosis, of the remaining 22 another 9 developed BM during follow up. PFS was also inferior for patients with BM at diagnosis with a median PFS of 4.3 months versus 9.0 without BM.Conclusion: In this real-world population of ROS1+ NSCLC patients, only half received primary treatment with TKI. Overall survival and PFS during TKI were disappointing, mainly related to brain metastasis. TKI treatment with agents that have intra-cranial activity may be beneficial in this patient population and our results confirm the importance of performing an MRI of the brain as part of the standard diagnostic work up in patients with ROS1+ NSCLC.

Automated summary

In patients with ROS1 rearrangement in the Netherlands, only half received primary treatment with TKI and the treatment outcomes were disappointing, mainly due to brain metastasis. Therefore, performing brain MRI as part of the standard diagnostic work up in patients with ROS1+ NSCLC is crucial.