Pneumologie 2020; 74(S 01): 131
DOI: 10.1055/s-0039-3403360
Posterbegehung (PO25) – Sektion Pneumologische Onkologie
NSCLC: Systemtherapie bei molekularem Treiber
Georg Thieme Verlag KG Stuttgart · New York

First-Line Therapy Using Brigatinib vs. Crizotinib in Patients With Advanced Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: Results From a Phase 3 Trial

MJ Hochmair
1   Otto Wagner Hospital, Vienna, Austria; Cois: None.; Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Department of Respiratory and Critical Care Medicine, Krankenhaus Nord
,
DR Camidge
2   University of Colorado; University of Colorado Cancer Center; Aurora
,
HR Kim
3   Yonsei University Severance Hospital
,
MJ Ahn
4   Samsung Medical Center
,
JCH Yang
5   National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan; Cois: Advisory Board Participation for, and Honoraria From, Astrazeneca, Roche/Genentech, Boehringer Ingelheim, Msd, Merck Serono, Novartis, Clovis Oncology, Eli Lilly, Bayer, Celgene, Astellas, Innopharma and Ono Pharmaceutical.; National Taiwan University Hospital
,
J Youn Han
6   National Cancer Center Korea; National Cancer Center
,
KH Lee
7   Chungbuk National University Hospital
,
A Delmonte
8   Scientific Institute of Romagna for the Study and Treatment of Cancer
,
MR Garcia Campelo
9   Complejo Hospitalario Universitario A Coruna Hospital Teresa Herrera-Materno Infantil
,
DW Kim
10   Seoul National University Hospital
,
F Griesinger
11   Pius-Hospital Oldenburg, University of Oldenburg
,
E Felip
12   Hospital Universitari Vall Dʼhebron; Medical Oncology; Vall Dʼhebron Institute of Oncology (Vhio)
,
R Califano
13   The Christie NHS Foundation Trust
,
A Spira
14   Virginia Cancer Specialists, Pc; Virginia Cancer Specialists
,
S Gettinger
15   Yale Cancer Center; Yale Cancer Center
,
M Tiseo
16   University Hospital of Parma
,
Q Ni
17   Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited
,
P Zhang
17   Millennium Pharmaceuticals, Inc., A Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited
,
S Popat
18   Royal Marsden Hospital
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Publikationsverlauf

Publikationsdatum:
28. Februar 2020 (online)

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Background: We report results from the first interim analysis of brigatinib vs. crizotinib in ALK TKI-naive, ALK+ NSCLC from ALTA-1L (NCT02737501).

Methods: This open-label, multicenter study enrolled patients with advanced ALK+ NSCLC who had ≤ 1 prior systemic therapy; asymptomatic CNS metastases were allowed. 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 ORR, intracranial (i) ORR (iORR), and PFS (iPFS). Interim analyses were planned at 50% and 75% of 198 expected PFS events.

Results: 275 patients were randomized (brigatinib/crizotinib, n = 137/138); median age: 58/60 y. 26%/27% received prior chemotherapy for advanced disease; 29%/30% had baseline brain metastases. At data cutoff (19 Feb 2018) for the first interim analysis, median follow-up of brigatinib/crizotinib was 11.0/9.25 mo. 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 median PFS (95% CI) was not reached (NR; NR) vs. crizotinib 9.8 months (9.0 – 12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30 – 0.68); log-rank P = 0.0001. Confirmed ORR for brigatinib was 71% (62 – 78) vs. crizotinib 60% (51 – 68). In patients with any iCNS disease (brigatinib/crizotinib, n = 43/47), confirmed iORR was 67% (51 – 81) vs. 17% (8 – 31); P < 0.0001. Brigatinib median iPFS was NR (11 mo-NR) vs. crizotinib 6 mo (4 – 9); HR 0.27 (95% CI 0.13 – 0.54); log-rank P < 0.0001. In patients with measurable iCNS disease (brigatinib/crizotinib, n = 18/21), confirmed iORR was 78% (52 – 94) vs. 29% (11 – 52); P = 0.0028. Most common grade ≥ 3 TEAEs for brigatinib: increased CPK (16.2%) and lipase (13.2%), hypertension (9.6%); for crizotinib, increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis (brigatinib/crizotinib): 3.7%/2.2%. Discontinuations due to AE (brigatinib/crizotinib): 11.8%/8.8%. Updated data from the second interim analysis will be presented.

Conclusions: Brigatinib showed a statistically and clinically significant improvement in PFS vs. crizotinib in patients with ALK inhibitor-naive ALK+ NSCLC.