Brain
metastasis is common in
non-small-cell lung cancer (NSCLC) with driver gene mutations.
Anaplastic lymphoma kinase (ALK) gene rearrangement is one of the common driver mutations in NSCLC.
Tyrosine kinase inhibitor (TKI) has been the research hotspot at present. However, there are relatively few studies specified on the treatment of brain
metastasis from ALK gene rearrangement NSCLC. The prognosis of these patients, the role of ALK-TKI, and the proper combination model of ALK-TKI with
radiotherapy are worth further exploring. This review focuses on new data on the prognosis of ALK-TKI and the proper combination model of ALK-TKI with
radiotherapy.
SUMMARY: According to some retrospective trials, for ALKi-naïve ALK rearrangement NSCLC patients with brain
metastasis,
crizotinib together with
radiotherapy seem to improve intracranial control rate, progression-free survival, and very likely improve overall survival; next-generation ALK-TKIs are now replacing
crizotinib as first-line treatment. For patients with central nervous system progression during
crizotinib application, combining
radiotherapy could improve the local control rate while continuing
crizotinib to control systemic disease. Second-/third-generation ALK inhibitors had higher intracranial ORR and DCR even after
crizotinib-refractory situations, and they alone had a strong efficacy against intracranial
tumors, in which situation
radiotherapy might be omitted. Stereotactic radiosurgery (SRS) and whole-brain
radiotherapy (WBRT) were both local treatment options for brain
metastasis, and the preferred choice was hard to make. ALK resistance is complicated with a wide range of molecular changes, and future studies are needed to solve these problems. Anyway, further and larger prospective studied are worth exploring to offer a confirmed preferred choice of drugs and radiation. Key Messages: Next-generation ALK-TKIs are now replacing
crizotinib as first-line treatment in ALKi-naïve ALK rearrangement NSCLC patients with brain
metastasis, and they alone might have a strong efficacy against intracranial
tumors in
crizotinib-refractory situations in which occasion
radiotherapy might be omitted. SRS and WBRT are both local treatment options for brain
metastasis.