LBA4 - Evaluation of anaplastic lymphoma kinase (ALK) inhibitor brigatinib [AP26113] in patients (Pts) with ALK+ non–small cell lung cancer (NSCLC) and b...

Date 16 April 2015
Event ELCC 2015
Session Medical and radiation oncology
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter David Kerstein
Citation Annals of Oncology (2015) 0 (0): 1-8. 10.1093/annonc/mdv128
Authors D. Kerstein1, S. Gettinger2, K. Gold3, C.J. Langer4, A.T. Shaw5, L.A. Bazhenova6, R. Salgia7, M.G. Conlan1, D.J. Dorer8, D..R. Camidge9
  • 1Clinical Research, ARIAD Pharmaceuticals, Inc., 02139 - Cambridge/US
  • 2Thoracic Oncology Program, Yale University School of Medicine Medical Oncology, 06520-8032 - New Haven/US
  • 3Department Of Thoracic/head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 4Abramson Cancer Center, University of Pennsylvania, Philadelphia/US
  • 5Massachusetts General Hospital Cancer Center, Harvard Medical School, 02114 - Boston/US
  • 6Moores Cancer Center, University of California San Diego, San Diego/US
  • 7Thoracic Oncology, The University of Chicago Medical Centre, Chicago/US
  • 8Biostatistics, ARIAD Pharmaceuticals, Inc., Cambridge/US
  • 9Thoracic Oncology, University of Colorado Cancer Center, Aurora/US

Abstract

Aim/Background

Central nervous system (CNS) progression has been observed in a substantial proportion of pts treated with crizotinib for ALK+ NSCLC. We report efficacy and safety of brigatinib, an investigational, oral tyrosine kinase inhibitor with preclinical activity against ALK and a broad range of crizotinib-resistant mutants, in ALK+ NSCLC pts with baseline (BL) intracranial CNS metastases.

Methods

In this phase 1/2 single-arm, multicenter study (NCT01449461), pts with advanced malignancies received brigatinib 30–300 mg orally once daily. Pts had BL contrast-enhanced MRI of the brain. BL and follow-up brain MRI scans in ALK+ NSCLC pts with intracranial CNS metastases were centrally reviewed by blinded independent neuroradiologists. This post hoc analysis was restricted to intracranial CNS lesions. Measurable lesions were defined as those with longest diameter ≥10 mm; history of local therapy did not inform the analysis.

Results

79 pts with ALK+ NSCLC enrolled in the trial; 46 were identified with brain metastases at BL (42 with prior crizotinib; 4 crizotinib-naive). 38 of the 46 pts were independently evaluated by abstract deadline and included in the efficacy analysis here; updated data will be presented. Median time on study was 51.4 weeks (n = 46).

The most common treatment-emergent adverse events in the pts with BL brain metastases were diarrhea, 24 pts (52%); nausea, 24 pts (52%); and fatigue, 23 pts (50%).

Conclusions

Brigatinib demonstrated significant intracranial antitumor activity with durable responses in ALK+ NSCLC pts with BL CNS metastases in this study. A prospective evaluation of brigatinib in ALK+ NSCLC pts with brain metastases is under way as part of the phase 2 ALTA study.

We acknowledge Glen Weiss, MD for his contributions to the study.

Disclosure

D. Kerstein, D.J. Dorer and M.G. Conlan: employment and equity ownership (ARIAD)

S. Gettinger: consultancy, research funding, & honoraria (ARIAD)

C.J. Langer: research funding (ARIAD)

A.T. Shaw: consultancy (ARIAD)

D.R. Camidge: research funding & honoraria (ARIAD)

All other authors have declared no conflicts of interest.