Brigatinib versus crizotinib in patients with ALK inhibitor-naive advanced ALK plus NSCLC: results from the phase 3 ALTA-1L trial
Califano, Raffaele Camidge, D. Kim, H. R. Ahn, M. J. Yang, J. Han, J. Y. Hochmair, M. Lee, K. H. Delmonte, A. Campelo, M. R. G.
Califano, Raffaele
Camidge, D.
Kim, H. R.
Ahn, M. J.
Yang, J.
Han, J. Y.
Hochmair, M.
Lee, K. H.
Delmonte, A.
Campelo, M. R. G.
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Abstract
Introduction: We report results of the first interim analysis from
the ALTA-1L study of brigatinib vs crizotinib in ALK TKI–naive, ALK+
NSCLC (NCT02737501).
Methods: This open-label, multicenter study enrolled patients with
stage IIIB/IV ALK+ NSCLC based on local ALK testing (FDA approved/
other). Eligible patients had ECOG PS 0–2, ≤1 prior systemic therapy
for locally advanced/metastatic NSCLC, and no prior ALK inhibitor.
Asymptomatic CNS metastases were allowed. All patients had
systematic CNS imaging. Patients were randomized 1:1 to brigatinib
180 mg QD with 7-day lead-in at 90 mg or crizotinib 250 mg BID.
Primary endpoint: blinded independent review committee (BIRC)-
assessed PFS (RECIST v1.1). Secondary efficacy endpoints included
BIRC-assessed objective response rate (ORR), intracranial ORR
(iORR), and intracranial PFS (iPFS). Interim analyses were planned at
50% and 75% of planned PFS events (n=198).
Results: 275 patients were randomized (brigatinib/crizotinib,
n=137/138); median age (years) 58/60. 26%/27% received prior
chemotherapy for advanced disease, and 29%/30% had baseline
brain metastases. At data cutoff (19 February 2018), median followup
brigatinib/crizotinib: 11.0/9.25 months; with 99 PFS events,
brigatinib met the prespecified threshold for statistical superiority
vs crizotinib in the primary endpoint, BIRC-assessed PFS (HR 0.49,
95% CI 0.33–0.74, log-rank p=0.0007); brigatinib mPFS was not
reached (95% CI NR–NR) vs crizotinib 9.8 months (95% CI 9.0–12.9).
Investigator-assessed PFS HR 0.45 (95% CI 0.30–0.68), log-rank
p=0.0001. Table 1 shows additional efficacy data. Most common
treatment-emergent AEs grade ≥3: brigatinib: increased CPK
(16.2%), increased lipase (13.2%), hypertension (9.6%); crizotinib:
increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/
pneumonitis: brigatinib, 3.7%; crizotinib, 2.2%. Discontinuations
due to AE (brigatinib/crizotinib): 11.8%/8.8%. Updated data from the second interim analysis will be presented. Conclusion: Brigatinib showed a statistically and clinically
significant improvement in PFS vs crizotinib in ALK inhibitor–naive
ALK+ NSCLC.
Affiliation
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Califano R, Camidge D, Kim HR, Ahn MJ, Yang J, Han JY, et al. Brigatinib versus crizotinib in patients with ALK inhibitor-naive advanced ALK plus NSCLC: results from the phase 3 ALTA-1L trial. Lung Cancer. 2020;139:S59-S60