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Poster Discussion session - NSCLC, metastatic 1

2521 - Intracranial efficacy of brigatinib (BRG) vs crizotinib (CRZ) in the phase 3 ALTA-1L trial


19 Oct 2018


Poster Discussion session - NSCLC, metastatic 1


Targeted Therapy

Tumour Site


Sanjay Popat


S. Popat1, H.R. Kim2, M. Ahn3, J.C. Yang4, J. Han5, M.J. Hochmair6, K.H. Lee7, A. Delmonte8, M.R. Garcia Campelo9, D. Kim10, F. Griesinger11, E. Felip12, R. Califano13, A.I. Spira14, S. Gettinger15, M. Tiseo16, J. Haney17, D. Kerstein18, D.R. Camidge19

Author affiliations

  • 1 Medical Oncology, Royal Marsden Hospital, SW3 6JJ - London/GB
  • 2 Division Of Medical Oncology, Department Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 03799 - Seoul/KR
  • 3 N/a, Samsung Medical Center, Seoul/KR
  • 4 Department Of Oncology, National Taiwan University Hospital, Taipei/TW
  • 5 Center For Lung Cancer, National Cancer Center, 10408 - Goyang/KR
  • 6 N/a, Department of Respiratory and Critical Care Medicine and Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Vienna/AT
  • 7 Internal Medicine, Chungbuk National University Hospital, 28644 - Cheongju/KR
  • 8 N/a, Scientific Institute of Romagna for the Study and Treatment of Cancer, Meldola/IT
  • 9 N/a, Complejo Hospitalario Universitario A Coruna Hospital Teresa Herrera-Materno Infantil, oruna/ES
  • 10 N/a, Seoul National University Hospital, Seoul/KR
  • 11 N/a, Pius-Hospital Oldenburg, Oldenburg/DE
  • 12 Medical Oncology Service (lung Cancer Unit)  , Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 13 Department Of Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 14 N/a, Virginia Cancer Specialists, Fairfax/US
  • 15 N/a, Yale Cancer Center, 06520-8032 - New Haven/US
  • 16 Medical Oncology, University Hospital of Parma, 43126 - Parma/IT
  • 17 Biostatistics, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge/US
  • 18 Clinical research, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge/US
  • 19 Cancer Center, University of Colorado Cancer Center, Aurora/US


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Abstract 2521


BRG, a next-generation ALK inhibitor, has robust efficacy in CRZ-resistant ALK+ NSCLC. ALTA-1L evaluated the efficacy of BRG vs CRZ in TKI-naive ALK+ NSCLC patients (pts). The primary endpoint of blinded independent review committee (BIRC)-assessed PFS was met at first interim analysis (IA) and previously reported (HR, 0.49; P=0.0007). Here we report detailed intracranial efficacy from the first IA of ALTA-1L (NCT02737501).


The open-label, multicenter study enrolled pts with ALK inhibitor-naive stage IIIB/IV ALK+ NSCLC. Pts were stratified by presence of baseline (BL) brain metastases and history of chemotherapy for advanced disease and randomized 1:1 to BRG 180 mg qd with 7-day lead-in at 90 mg or CRZ 250 mg bid. Primary endpoint: BIRC–assessed PFS (RECIST v1.1). IAs were planned at ~50% and ~75% of 198 expected PFS events. Secondary endpoints included intracranial ORR (iORR) and intracranial PFS (iPFS). An exploratory competing risks analysis of intracranial progression (per CNS BIRC), systemic progression (per systemic BIRC), and death was also performed.


Of 275 randomized pts (BRG/CRZ, n=137/138), 31%/34% had BL brain metastases (BIRC-assessed); 13%/14% had prior brain radiotherapy. At data cut-off (19 February 2018; median follow-up, 11/9.3 mo), iPFS in ITT population was significantly improved with BRG (HR, 0.42 [95% CI, 0.24–0.70]; P=0.0006). In the ITT population competing risks analysis, time to intracranial progression without prior systemic progression was significantly improved with BRG (HR, 0.30 [95% CI, 0.15–0.60]; P<0.001); 1-year cumulative incidence (BRG vs CRZ): 12% (95% CI, 6–20) vs 23% (95% CI, 15–31). Time to systemic progression without prior intracranial progression was also improved with BRG (HR, 0.51 [95% CI, 0.30–0.86]; P=0.017). Additional intracranial efficacy results are presented in the Table.


BRG has superior intracranial activity vs CRZ in ALK TKI-naive pts with ALK+ NSCLC.

BIRC-Assessed Endpoint BRG CRZ P Value

All patients (ITT), n

137 138
iPFS events, n (%) 22 (16) 39 (28)
Median iPFS, mo NR (NRa) NR (11–NRa)
1-y iPFS, % 78 (68–85a) 61 (50–71a)
iPFS hazard ratio (95% CI) 0.42 (0.24–0.70a) 0.0006b
Any baseline brain metastases, n 43 47
iPFS events, n (%) 11 (26) 28 (60)
Median iPFS, mo NR (11–NRa) 6 (4–9a)
1-y iPFS, % 67 (47–80a) 21 (6–42a)
iPFS hazard ratio (95% CI) 0.27 (0.13–0.54a) <0.0001b
iORRc, % 79 (64–90a) 23 (12–38a) <0.0001d
Confirmed iORR, % 67 (51–81a) 17 (8–31a) <0.0001d
Measurable brain metastases, n 18 21
iORRc, % 83 (59–96a) 33 (15–57a) 0.0023d
Confirmed iORR, % 78 (52–94a) 29 (11–52a) 0.0028d

NR, not reached

a95% CI; bLog-rank; cResponse, ≥1 assessment; dCochran-Mantel-Haenszel test

Clinical trial identification

NCT02737501; March 30, 2016

Editorial Acknowledgement

Professional medical writing assistance was provided by Lauren Gallagher, PhD, of Peloton Advantage, LLC, Parsippany, New Jersey, USA, and funded by Millennium Pharmaceuticals, Inc.

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