Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis

Abstract

Purpose: We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis.

Patients and methods: A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling.

Results: Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001).

Conclusion: Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs 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 SRS, close CNS observation, and treatment of emergent CNS disease.

Fig 1.

Kaplan-Meier estimate of (A) overall (OS) and (B) intracranial progression-free survival (IC PFS) from date of diagnosis of brain metastasis.

Fig 2.

Kaplan-Meier estimate of overall survival from date of diagnosis of brain metastasis, stratified by (A) presence or absence of extracranial metastasis (ECM) at time of brain metastases diagnosis, (B) Karnofsky performance score (KPS) at time of brain metastasis diagnosis, and (C) number of brain metastases at time of diagnosis.

Fig 3.

Kaplan-Meier estimate of (A) overall (B) and intracranial progression-free survival from date of diagnosis of brain metastasis, stratified by treatment with tyrosine kinase inhibitor (TKI) before development of brain metastasis or initiation of TKI after diagnosis of brain metastasis.

Fig 4.

(A) Kaplan-Meier estimates of overall survival for patients with brain metastases and ALK rearrangement and zero, one, two, or three positive prognostic risk factors. (B) Prevalence of brain interventions in this patient cohort. Number of patients receiving at least one, two, three, or four radiotherapy (blue) or craniotomy (gold) interventions is presented.

Fig A1.

Kaplan-Meier estimate of (A) overall and (B) intracranial progression-free survival from the date of diagnosis of brain metastasis, stratified by initial type of radiotherapy as treatment for brain metastasis. SRS, stereotactic radiosurgery; WBRT, whole-brain radiotherapy.