The median progression-free survival rates were 19.3 months with brigatinib and 19.2 months with alectinib in the phase 3 ALTA-3 study for patients with ALK-positive non–small cell lung cancer.
Progression-free survival (PFS) results with brigatinib (Alunbrig) were not superior to that observed with alectinib (Alecensa) in crizotinib (Xalkori)-pretreated patients with ALK-positive non–small cell lung cancer (NSCLC), according to findings from the phase 3 ALTA-3 study (NCT03596866).1
Though brigatinib was not superior vs alectinib in regard to survival, safety data between the 2 were consistent.
In the open-label, phase 3 trial ALTA-3 study, investigators evaluated the efficacy and safety of brigatinib compared with alectinib for the treatment of patients with ALK-positive NSCLC after disease progression on crizotinib. The trial randomized patients 1:1 to brigatinib 180 mg once daily (7-day lead-in, 90 mg) or alectinib 600 mg twice daily. Investigators aimed to test superiority.
The primary end point of the study was PFS assessed by blinded independent review committee (BIRC). Secondary end points of the study included overall survival (OS), PFS, objective response rate (ORR), duration of response (DOR), time to response as assessed by BIRC, intracranial ORR, intracranial DOR, time to intracranial disease progression, and health-related quality of life.2
Patients eligible for enrollment in the study were those aged 18 years and older with histologically or cytologically confirmed stage IIIB or stage IV NSCLC with ALK rearrangement determined by a positive result from the Vysis ALK Break-Apart fluorescence in situ hybridization Probe Kit or the Ventana ALK (D5F3) CDx Assay or Foundation Medicine's FoundationOne CDx or by a different test for which a tumor sample could be provided to the central laboratory.
Patients must have had progressive disease while on crizotinib, received crizotinib for at least 4 weeks before progression, have had no other ALK inhibitor other than crizotinib, and had no more than 2 prior regimens of systemic anticancer therapy. Additionally, patients must have had at least 1 measurable lesion per RECIST v1.1., have recovered from toxicities related to prior anticancer therapy, have adequate organ function, and suitable venous access for study-required blood sampling.
A total of 248 were enrolled in the study, including 125 who received brigatinib, and 123 who were treated with alectinib.1 The median duration of prior crizotinib ranged between 16.0-16.8 months. Patients had a low rate of ALK fusion in baseline circulating tumor DNA (ctDNA; 34%).
Findings showed that the median BIRC-assessed PFS with brigatinib was 19.3 months vs 19.2 months with alectinib (HR, 0.97; 95% CI, 0.66-1.42; P =.8672]), and the study met futility criterion. At this time, the OS data were immature with 41 events (17%).
Looking at exploratory analyses pooled across treatment groups, the median PFS was 11.1 in patients with ctDNA-detectable ALK fusions vs 22.5 months in patients without ctDNA-detectable ALK fusion at baseline (HR, 0.48; 95% CI, 0.32-0.71).
Moreover, safety data showed that treatment-related adverse events seen in >30% of patients treated with brigatinib or alectinib included elevated blood creatine phosphokinase (70% v 29%), aspartate aminotransferase (53% v 38%), and alanine aminotransferase (40% v 36%).