ALK-Rearranged NSCLC With Brain Metastases Shows Prolonged Survival

Patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and brain metastases survive longer when treated with radiotherapy and tyrosine kinase inhibitors (TKIs), according to a new study. The results suggest control of intracranial disease is important in these patients.

Approximately 30% of patients with advanced lung adenocarcinomas develop central nervous system metastases; they are particularly common among those with ALK rearrangement. “Control of metastatic disease to the brain is now emerging as a crucial issue in the treatment of these patients, and it has been suggested that local control of disease at sites of oligoprogression may improve outcomes,” wrote study authors led by Joseph N. Contessa, MD, PhD, of Yale University School of Medicine in New Haven, Connecticut.

The study included 90 patients with brain metastases from ALK-rearranged NSCLC; 84 of them received radiotherapy to the brain (either stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 received TKI therapy. The results were published in the Journal of Clinical Oncology.

The median overall survival after brain metastasis development was 49.5 months, with a median intracranial progression-free survival of 11.9 months. At death, 45% of patients with follow-up had progressive brain metastases.

Several factors were associated with improved survival, including the absence of extracranial metastases (ECM; P = .003), Karnofsky performance score (KPS) of 90 or above (P < .001), and no history of TKI therapy before development of brain metastases (P < .001). Single brain metastasis and SRS vs WBRT were not associated with any survival difference.

Patients with a KPS below 90, ECM, and prior TKI therapy had a 2-year survival rate of only 33%. The researchers also stratified patients into groups with one, two, or three of the positive prognostic factors, and the 2-year survival in these groups was 59%, 76%, and 100%, respectively (P < .001).

“On the basis of the data from this study, we make a strong recommendation to treat patients with either KPS ≥ 90, no ECM, or no prior TKI therapy with SRS,” the authors concluded. “As advances in the treatment of this disease are made with both local and systemic therapies, favorable SRS side effect profiles or other factors such as patient eligibility to receive effective systemic therapy may also warrant consideration of SRS over WBRT for treatment of brain metastases.”