Analysis of Intracranial Response to Brigatinib in ALK-Positive NSCLC With Brain Metastases


Key Points

  • Intracranial response was observed in more than half of patients with measurable metastases at baseline.
  • Intracranial progression-free survival was 14.6 to 18.4 months among all patients with baseline metastases.

In an analysis of two clinical trials reported in the Journal of Clinical Oncology, Camidge et al found that brigatinib (Alunbrig) produced high intracranial response rates and good intracranial progression-free survival in patients with ALK-positive non–small cell lung cancer (NSCLC) and brain metastases who had received prior crizotinib (Xalkori) therapy.

Study Details

The analysis involved patients with baseline brain metastases including 50 patients receiving brigatinib at a total of 90 to 240 mg daily in a phase I/II trial and 80 and 73 patients in arms A and B of the phase II ALTA trial receiving 90 mg once daily and 180 mg once daily after a 7-day lead-in at 90 mg daily. Among these patients, 46% in the phase I/II trial, 40% of ALTA arm A, and 41% of ALTA arm B had no prior brain radiotherapy. All patients except 4 in the phase I/II trial had received crizotinib.

Among patients with measurable (≥ 10 mm) brain metastases, confirmed intracranial objective response was observed in 8 (53%) of 15 in the phase I/II trial, 12 (46%) of 26 in ALTA arm A, and 12 (67%) of 18 in ALTA arm B. Response rates were similar in subgroups without prior radiation or progression postradiation. Among all patients with any baseline brain metastases, median intracranial progression-free survival was 14.6 months among those in the phase I/II trial, 15.6 months among those in ALTA arm A, and 18.4 months in ALTA arm B.

The investigators concluded, “Brigatinib yielded substantial intracranial responses and durable [intracranial progression-free survival] in ALK-positive, crizotinib-treated NSCLC, with highest [intracranial progression-free survival] in patients receiving 180 mg per day (with lead-in).”

The study was supported by ARIAD Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

D. Ross Camidge, MD, PhD, of the University of Colorado Cancer Center, Aurora, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.




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