OBJECTIVES: ROS1+ fusion are rare genetic abnormalities (~1-2%) in Non-Small Cell Lung Cancer (NSCLC) with select TKIs as guideline recommended therapy. This exploratory analysis examined real-world treatment patterns and potential limitations using US physician narratives of patient encounters.

METHODS: Natural language processing and manual abstractions were performed on electronic medical transcriptions of 29 million unique patients, 2015 to Nov 2021. Study population included NSCLC, ROS1+ patients, age >/= 18 years, and taking a US FDA approved or off-label TKI: crizotinib, entrectinib, ceritinib or lorlatinib.

RESULTS: Of the 103 ROS1+ patients identified, 25 received TKI. This treatment cohort was 52% female, 8% current smokers, mean age of 62 years. Crizotinib was the most frequently used TKI (23/25). Total time on first-line (1L) TKI ranged from 1 - <18 months. In patients who completed their 1L TKI, majority were on crizotinib and 44% for 6 - <18 months (n=8); 39% for <6 months (n=7). Only 7 patients taking second-line TKI, most for <6 months. Majority of patients (22/33) experienced treatment disruptions on TKIs. For crizotinib, 65% experienced disruptions (30% hold, 43% stop or switch, 17% dose reduction). Across all TKIs, 50% of patients experienced disruption within 3 months, 39% were holds, 26% dose reduction, 30% switch, and 4% discontinuation. Most common reasons for TKI disruptions were progression (53%) and tolerability/adverse effects (AE) (40%). Progression was noted in 53% (8) of crizotinib patients. Tolerability/AE issues in crizotinib users were diverse and non-specific such as decreased appetite/weight loss, elevated liver enzymes, fatigue, thrombocytopenia, correcting QTC.

CONCLUSIONS: Time on TKI therapy varied considerably with majority of patients experiencing early treatment disruptions. Results suggest possible unmet need among ROS1+ NSCLC patients using contemporary TKIs since treatment disruptions can occur within 3 months of initiation, use may be sporadic, and many patients experience disease progression and tolerability issues.