PROGNOSTIC FACTORS FOR ALK+ NSCLC

In a study reported in the Journal of Clinical Oncology, Johung and colleagues identified factors that distinguished survival rates among patients with ALK-rearranged non–small cell lung cancer (NSCLC) and brain metastasis.

The study included 90 patients from six institutions. Of them, 84 patients had received radiotherapy to the brain, consisting of stereotactic radiosurgery or whole-brain radiotherapy, and 86 patients had received tyrosine kinase inhibitor therapy (crizotinib [Xalkori] in 84 and a second-generation tyrosine kinase inhibitor in 41).

Prognostic Factors

Median overall survival after development of brain metastases was 49.5 months, and median intracranial progression-free survival was 11.9 months. Overall, 45% of patients with follow-up had progressive brain metastases at death.

The absence of extracranial metastases (P = .003), Karnofsky performance score ≥ 90 (P = .001), and no history of tyrosine kinase inhibitors before development of brain metastases (P = .001) were associated with improved overall survival. The presence of a single brain metastasis (P = .633) and initial treatment with stereotactic radiosurgery vs whole-brain radiotherapy (P = .666) were not associated with survival.

On multivariate analysis, no prior treatment with ALK-targeted tyrosine kinase inhibitors (hazard ratio [HR] = 0.382, P = .045), absence of extracranial metastasis (HR = 0.241, P = .029), and Karnofsky performance score ≥ 90 (HR = 0.191, P = .042, vs Karnofsky performance score  < 70) were independent positive predictors of overall survival. Estimated 2-year overall survival was 33% among patients with tyrosine kinase inhibitor therapy prior to development of brain metastasis, extracranial metastasis, and Karnofsky performance score < 90, compared with 59%, 76%, and 100% among patients with one, two, and three positive prognostic factors (P < .001). 

The investigators concluded: “Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (stereotactic radiosurgery and/or whole-brain radiotherapy) and tyrosine kinase inhibitors have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line stereotactic radiosurgery, close CNS observation, and treatment of emergent CNS disease.”