Characteristics of Short-Term Survivors With ALK or ROS1-Altered Metastatic NSCLC

The prognostic significance of baseline and on-treatment brain and liver metastasis in ALK+ or ROS1+ metastatic NSCLC (mNSCLC) remains unclear. As we consider intensification strategies, it is critical to identify factors that predict high-risk disease.

Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with ALK+ or ROS1+ mNSCLC. Baseline characteristics and the cumulative incidence (CI) of brain and liver metastases were compared (≥2-year survivors versus <2-year; pre-2017 versus post-2017). Multivariable Cox proportional hazard models were used to evaluate the association between factors and overall survival, and multivariable logistic regression models were used for the odds of death within 2 years.

A total of 310 patients with ALK+ mNSCLC were identified (≥2-y: 229, <2-y: 81). There was no difference in cumulative incidence of brain metastases between survival groups (29% at 21 mo). However, the cumulative incidence of liver metastasis was higher in those who survived less than 2 years (20.9% versus 5.4% at 21 mo). The cumulative incidence of brain but not liver metastases has improved post-2017 with the newer generation of ALK tyrosine kinase inhibitors. There were 69 patients with ROS1+ mNSCLC who were identified (≥2-y: 46, < 2-y: 23). There was no significant difference in the cumulative incidence of brain or liver metastases between less-than-2-year and greater-than-or-equal-to-2-year survivor cohorts (p = 0.664, p = 0.201).

Among patients with ALK+ but not ROS1+ mNSCLC, the presence of liver metastases at baseline and on-treatment was associated with worse survival. In the ALK+ population, the cumulative incidence of brain but not liver metastases is improving, highlighting a need for therapies effective at the treatment and prevention of liver metastases.