Brigatinib (BRG) vs crizotinib (CRZ) in anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-naive ALK plus non-small cell lung cancer (NSCLC): ALTA-1L final results
Tiseo, M. Popat, S. Kim, H. R. Ahn, M. J. Yang, J. C. Han, J. Y. Hochmair, M. J. Lee, K. H. Delmonte, A. Campelo, M. R. G.
Tiseo, M.
Popat, S.
Kim, H. R.
Ahn, M. J.
Yang, J. C.
Han, J. Y.
Hochmair, M. J.
Lee, K. H.
Delmonte, A.
Campelo, M. R. G.
Citations
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Abstract
Background
In ALTA-1L planned interim analyses, BRG progression-free survival (PFS) by blinded independent review committee (BIRC) was superior to CRZ. We report final ALTA-1L (NCT02737501) results.
Methods
Patients (pts) were randomized 1:1 to BRG 180 mg qd (7-day lead-in at 90 mg) or CRZ 250 mg bid. Primary endpoint: PFS by BIRC. Secondary endpoints included intracranial PFS (iPFS; BIRC), overall survival (OS), safety, quality of life (QoL).
Results
275 pts randomized (BRG/CRZ, n=137/138); median age 58/60 y; prior chemotherapy (CT) 26%/27%; median CT duration, 71/73 days; baseline brain metastases (BL BM) 29%/30%. As of 29 Jan 2021 (last patient contact), median follow-up was 40.4/15.2 mo, with 166 (73/93) PFS events. BIRC PFS hazard ratio (HR) was 0.48 (95% CI: 0.35–0.66, log-rank P<0.0001); median PFS was 24.0 (95% CI: 18.4–43.2)/11.1 (9.1–13.0) mo; 3-yr PFS rate, 43%/19%. PFS HR by investigator was 0.43 (0.31–0.58; median PFS 30.8 vs 9.2 mo). Median duration of response (DoR) was 33/14 mo by BIRC and 37/11 mo by investigator. Median OS was not reached in either group (events: 41/51; HR 0.81 [0.53–1.22]; 3-yr OS 71%/68%. In pts with BL BM, PFS HR 0.25 (0.14–0.46); OS HR 0.43 (0.21–0.89; Table). Most common grade ≥3 treatment-emergent adverse events (AE): BRG: increased creatine phosphokinase (26%) and lipase (15%), hypertension (14%); CRZ: increased alanine aminotransferase (10%), lipase, (8%), aspartate aminotransferase (7%). Any-grade interstitial lung disease/pneumonitis: 5.9%/2.2%; discontinuation due to AE: 13.2%/8.8%. Median time to worsening in pt-reported global health status/QoL was 26.7/8.3 mo; HR 0.69 (0.49–0.98).
Table: 29P
Efficacya BRG CRZ P
BL brain metastases
Measurable, n 18 23
Confirmed iORR, % 78 (52–94b) 26 (10–48b) 0.0014c
Median iDoRd, mo 28 (6–NEb) 9 (4–NEb)
Any, n 40e 41e
PFS events, n (%) 24 (60) 31 (76)
HR 0.25 (0.14–0.46b) <0.0001f
OS events, n (%) 11 (28) 22 (54)
3-yr OS, % 74 (57–85b) 55 (38–69b)
HR 0.43 (0.21–0.89b) 0.0199f
47a 49a
iPFS events, n (%) 27 (57) 35 (71)
HR 0.29 (0.17–0.51b) <0.0001f
, n 97e 97e
PFS events, n (%) 49 (51) 62 (64)
HR 0.62 (0.43–0.91b) 0.0131f
OS events, n (%) 30 (31) 29 (30)
3-yr OS, % 70 (59–78b) 73 (62–81b)
HR 1.16 (0.69–1.93b) 0.6027f
90a 89a
iPFS events, n (%) 25 (28) 23 (26)
HR 0.70 (0.39–1.26b) 0.2410f
a BIRC; b 95% CI; c CMH test; d Confirmed responders; e Investigator; f Log-rank
Conclusions
BRG demonstrated durable overall and intracranial efficacy with manageable tolerability with extended treatment, confirming BRG as a standard of care in treatment-naive ALK+ NSCLC.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Tiseo M, Popat S, Kim HR, Ahn MJ, Yang JC, Han JY, et al. 29P Brigatinib (BRG) vs crizotinib (CRZ) in anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor-naive ALK+ non-small cell lung cancer (NSCLC): ALTA-1L final results. Vol. 33, Annals of Oncology. Elsevier BV; 2022. p. S44–5.