Systemic and intracranial efficacy of brigatinib vs.crizotinib: updated results from the ALTA-1L Trial
Popat, S. Kim, H. R. Ahn, M. J. Yang, J. C. H. Han, J. Y. Hochmair, M. Lee, K. H. Delmonte, A. Campelo, M. R. G. Kim, D. W.
Popat, S.
Kim, H. R.
Ahn, M. J.
Yang, J. C. H.
Han, J. Y.
Hochmair, M.
Lee, K. H.
Delmonte, A.
Campelo, M. R. G.
Kim, D. W.
Citations
Altmetric:
Abstract
Background: At ALTA-1L (NCT02737501) first interim analysis (IA1),
brigatinib demonstrated superior BIRC-assessed PFS and iPFS vs crizotinib.
We report IA2 results, planned at w75% of 198 expected PFS
events. Methods: Patients with TKI-naive advanced ALK+ NSCLC were
randomized 1:1 to brigatinib 180 mg qd (7-day lead-in at 90 mg) or
crizotinib 250 mg bid. Endpoints: Primary, BIRC-assessed PFS (RECIST
v1.1); secondary included confirmed ORR and iORR, and iPFS (BIRC).
Results: 275 patients were randomized (brigatinib/crizotinib, n¼137/
138); median age, 58/60 years; prior chemotherapy, 26%/27%;
baseline brain metastases (BIRC), 34%/36%; brain radiotherapy, 13%/
14% (WBRT/SRS balanced across arms). At data cutoff (28 June 2019,
median follow-up [brigatinib/crizotinib], 24.9/15.2 months, 150 PFS
events): BIRC-assessed PFS HR, 0.49 (95% CI, 0.35e0.68, log-rank
P<0.0001); brigatinib mPFS, 24.0 months (95% CI, 18.5eNE) vs crizotinib
11.0 months (9.2e12.9). Investigator-assessed PFS HR was 0.43
(95% CI, 0.31e0.61, median 29.4 vs 9.2 months). OS was immature
(total events: 33/37, brigatinib/crizotinib). In patients with baseline
brain metastases, PFS HR was 0.25; data were less mature in brigatinib
patients without brain metastases. Additional results in Table. Radiological
overall disease progression occurred in (brigatinib vs crizotinib)
54 (39%) vs 74 (54%) patients (BIRC) and 50 (36%) vs 84 (61%)
(investigator); of these, brain was first site of progression more
frequently with crizotinib vs brigatinib: 31 (42%) vs 17 (31%) patients
(BIRC); 22 (26%) vs 7 (14%) (investigator). Most common TEAEs
grade 3: brigatinib: increased CPK (24.3%) and lipase (14.0%), hypertension
(11.8%); crizotinib: increased ALT (10.2%), AST (6.6%),
lipase (6.6%). Brigatinib significantly delayed median time to deterioration
vs crizotinib for global health score/QoL (log-rank P¼0.0485),
emotional and social functioning, fatigue, nausea and vomiting, appetite
loss, constipation. Conclusions: Brigatinib demonstrated superior
systemic and intracranial efficacy vs crizotinib in all patients with TKInaive
ALK+ NSCLC and in patients with baseline brain metastases.
Affiliation
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Popat S, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair M, et al. Systemic and intracranial efficacy of brigatinib vs.crizotinib: updated results from the ALTA-1L Trial. Journal of Thoracic Oncology. 2021;16(1):S8-S9