Efficacy and safety of brigatinib after alectinib in patients with ALK-positive NSCLC: Integrated analysis of the ALTA-2 and J-ALTA studies.

OBJECTIVES

Alectinib is a first-line treatment for ALK + NSCLC. There is a lack of evidence guiding treatment after disease progression on alectinib. This integrated analysis of two phase 2 trials evaluated efficacy and safety of brigatinib in patients who had disease progression on prior alectinib.

MATERIALS AND

METHODS

ALTA-2 (NCT03535740) and J-ALTA (NCT03410108) were single-arm, multicenter, phase 2 trials of brigatinib in previously treated advanced/metastatic ALK + NSCLC. Patients receiving brigatinib 180 mg QD (with 7-day lead-in at 90 mg QD) post-alectinib in either trial were pooled for this analysis.

RESULTS

One hundred thirty-three patients received brigatinib after alectinib; among those, 58 % received alectinib as their first-line tyrosine kinase inhibitor. The objective response rate by independent review committee (IRC) was 31 % (95 % CI: 23 %-39 %); median duration of response was 9.2 months (95 % CI: 5.5-19.4). Median IRC-assessed progression-free survival (PFS) was 5.2 months (95 % CI: 3.7-7.3), and overall survival was 25.0 months (16.2-not reached). Of 131 patients with baseline plasma evaluable for next-generation sequencing, 61 % had ALK fusion detected in circulating tumor DNA (ctDNA). Patients ctDNA-negative for ALK fusion had longer PFS than those testing positive (11.0 versus 3.5 months; HR = 0.33, 95 % CI: 0.20-0.54, P < 0.0001). Brigatinib's safety profile was similar to previous reports. The most common adverse events were increased blood creatine phosphokinase (49 %), diarrhea (40 %), and nausea (32 %).

CONCLUSIONS

This integrated analysis showed that brigatinib has clinically meaningful activity after disease progression on alectinib.

STUDY REGISTRATION: ALTA-2 (ClinicalTrials.gov: NCT03535740); J-ALTA (ClinicalTrials.gov: NCT03410108).