‘Substantial’ Brigatinib Responses Reported For ALK-Rearranged NSCLC With Crizotinib Resistance

The phase II ALTA trial demonstrates a response to brigatinib in around half of patients with crizotinib-refractory non-small-cell lung cancer with an anaplastic lymphoma kinase rearrangement

medwireNews: The preliminary dose-finding results for brigatinib in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) refractory to crizotinib have been published in the Journal of Clinical Oncology.

The ALTA trial compared the oral next-generation ALK inhibitor at a daily dose of 90 mg (n=109) or 180 mg after an initial 7-day lead-in dose at 90 mg (n=110) for the primary endpoint of objective response rate (ORR), explain Dong-Wan Kim, from Seoul National University Hospital in South Korea, and co-investigators.

After a median of 8.0 months, investigator-assessed ORR was confirmed as 45% for the 90 mg/day dose and 54% for the 180 mg/day dose, with complete responses reported for 1% and 4%, respectively, and partial responses for 44% and 50%.

The disease control rates for the 90 mg and 180 mg groups were 82% and 86%, respectively, and the corresponding median progression-free survival rates were 9.2 and 12.9 months.

In addition, an independent review committee assessment of patients with brain metastases at baseline determined the intracranial ORR rate to be 42% of 26 patients given brigatinib 90 mg/day and 67% of 18 patients given the 180 mg/day dose.

Rates of treatment-emergent adverse events (AEs), mostly grades 1 or 2, were comparable in the two dose groups, and were most commonly nausea (33 and 40% of the 90 and 180 mg arms, respectively), diarrhoea (19 and 38%), headache (28 and 27%) and cough (18 and 34%).

The authors note that early-onset pulmonary adverse events – at a median of 2 days after beginning treatment – were reported in 6% of patients using a dose of 90 mg/day, mainly dyspnoea, hypoxia, cough, pneumonia and pneumonitis. This included grade 3 or more serious side effects in 3% of the group, although brigatinib was re-initiated in seven of the 14 affected patients.

“Patients treated with brigatinib should be monitored for new or worsening respiratory symptoms, particularly during the first week of treatment”, recommend Dong-Wan Kim et al. “Management of early pulmonary AEs should include dose interruption and prompt clinical evaluation.”

The researchers summarise: “Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed consistently better efficacy than 90 mg, with acceptable safety.”

They add: “Brigatinib is currently being investigated in a randomized, phase III trial of brigatinib (180 mg [with lead-in]) versus crizotinib in ALK inhibitor–naive patients (ALTA-1L).”


Kim D-W, Tiseo M, Ahn M-J, et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase–positive non–small-cell lung cancer: A randomized, multicenter phase II trial. J Clin Oncol; Advance online publication 5 May 2017. DOI: 10.1200/JCO.2016.71.5904

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