ALTA

ALTA (ALK in Lung Cancer Trial of AP26113) was a randomised phase 2 trial of brigatinib in ALK-positive non-small-cell lung cancer that had progressed on crizotinib. It randomised 222 patients 1:1 to brigatinib 90 mg once daily (arm A, 112 patients, 109 treated) or 180 mg once daily after a 7-day lead-in at 90 mg (arm B, 110 patients), stratified by brain metastases and best response to crizotinib. At baseline 69 percent had brain metastases and 74 percent had received chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate; there was no arm without brigatinib.

At a median follow-up of 8.0 months the confirmed response rate was 45 percent in arm A and 54 percent in arm B, and median progression-free survival was 9.2 and 12.9 months. Among patients with measurable brain metastases, independent review found intracranial responses in 11 of 26 (42 percent) and 12 of 18 (67 percent). Common adverse events were nausea, diarrhoea, headache and cough, mostly grade 1 or 2. A subset of pulmonary adverse events with early onset (median day 2) occurred in 14 of 219 treated patients (grade 3 or higher in 3 percent) and none occurred after escalation to 180 mg in arm B (Journal of Clinical Oncology 2017).

The authors concluded that 180 mg with the lead-in was consistently more effective than 90 mg with acceptable safety. The trial supported the 2017 US approval of brigatinib after crizotinib; ALTA-1L then tested it against crizotinib in untreated disease.