Brain metastases, treatment patterns, and outcomes in ROS1-positive NSCLC patients from US oncology community centers

As new targeted therapies with CNS penetration and activity for non-small cell lung cancer (NSCLC) with ROS1 gene fusions (ROS1+) emerge, there is a need to characterize the disease course of patients (pts) receiving current treatment, especially in relation to CNS metastases (met).

We evaluated an anonymized cohort of ROS1+ NSCLC pts from the Flatiron Health electronic health record (EHR)-derived database of US cancer centers (2011–2018). Descriptive statistics were used for clinical and treatment pattern characterization. Kaplan-Meier curves estimated median overall survival (OS), real-world progression-free survival (rwPFS, using physician documentation in the EHR) and rwPFS in the CNS, from 1st-line treatment (1L) after diagnosis of advanced/metastatic NSCLC (aNSCLC Dx). Due to low numbers of pts in some groups, 95% CI are not reported.

We identified 129 ROS1+ aNSCLC pts who received 1L treatment including crizotinib (n = 52, 40.3%), chemotherapy (n = 34, 26.4%), combination systemic therapy (n = 25, 19.4%), clinical study drug (n = 4, 3.1%), or no treatment (n = 14, 10.9%). For 1L crizotinib (the only approved therapy for ROS1+ NSCLC) after aNSCLC Dx median rwPFS: 8.6 m (95% CI: 6.2–12.1); OS: 19.9 m (95% CI: 15.1–NR). For pts receiving other 1L drugs median rwPFS: 5.9 m (95% CI: 4.1–7.2); OS: 18.1 m (95% CI: 12.9–34.6). There were 24 pts (18%) with CNS met at diagnosis and 20 pts (19%) at follow-up. Most pts with CNS met at or after diagnosis received surgery/radiotherapy (37/44, 84.1%). For CNS met pts who received 1L crizotinib after local treatment (6/11), median rwPFS: 8.0 m; OS: 27 m. From 1L crizotinib, pts with CNS met at follow-up only (10/21 pts with CNS mets who received 1L crizotinib), median rwPFS: 7.2 m; rwPFS-CNS: 9.1 m; OS: 15.1 m. For pts with no CNS mets anytime median rwPFS: 10.0 m; OS: 21.5 m from 1L crizotinib (34/55 pts).

In the US, ROS1+ NSCLC pts receive various 1L treatments after aNSCLC Dx. CNS was a site of metastasis in 44/129 ROS1+ NSCLC pts. Surgery/radiotherapy for CNS mets prior to systemic therapy appeared to result in favorable outcomes, however conclusions on the natural history of cancers with rare mutations rely on very small patient numbers.