1293P - Evaluation of ceritinib-treated patients (pts) with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) and brain metas...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Pathology/Molecular Biology
Translational Research
Non-Small Cell Lung Cancer
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Alice Shaw
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors A. Shaw1, R. Mehra2, D.S.W. Tan3, E. Felip4, L.Q. Chow5, D.R. Camidge6, J.F. Vansteenkiste7, S. Sharma8, T. De Pas9, G.J. Riely10, B. Solomon11, J. Wolf12, M. Thomas13, M. Schuler14, G. Liu15, A. Santoro16, M. Geraldes17, A.L. Boral18, A. Yovine19, D. Kim20
  • 1Massachusetts General Hospital Cancer Center, Harvard Medical School, 02114 - Boston/US
  • 2Medical Oncology, Fox Chase Cancer Center, 19111 - Philadelphia/US
  • 3Department Of Medical Oncology, National Cancer Center, Singapore/SG
  • 4Head Thoracic Oncology Unit, Oncology Department, Vall D'Hebron University Hospital, 08035 - Barcelona/ES
  • 5Department Of Medicine, University of Washington, 98109 - Seattle/US
  • 6Medicine, University of Colorado, Denver/US
  • 7Respiratory Oncology Unit (pulmonology), University Hospital KU Leuven, 3000 - Leuven/BE
  • 8Medical Oncology, Huntsman Cancer Institute, US-84112 - Salt Lake City/US
  • 9Thoracic Medical Oncology, European Institute of Oncology, 20121 - Milan/IT
  • 10Medicine, Memorial Sloan-Kettering Cancer Center, New York/US
  • 11Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne/AU
  • 12Department I Of Internal Medicine, Center For Integrated Oncology, University of Cologne, 50924 - Cologne/DE
  • 13Department Of Thoracic Onkology, Thoraxklinik, University of Heidelberg, Heidelberg/DE
  • 14German Cancer Consortium, Heidelberg, University Hospital Essen, University Duisburg-Essen, Essen/DE
  • 15Medical Biophysics, Princess Margaret Cancer Centre, Ontario Cancer Institute, M5G2M9 - Toronto/CA
  • 16Medical Oncology And Hematology, Humanitas Cancer Center, 20089 - Rozzano-Milan/IT
  • 17Novartis Pharmaceuticals Corporation, Novartis Pharmaceuticals Corporation, 07936 - East Hanover/US
  • 18Oncology Translational Medicine, Novartis Institutes for BioMedical Research, Cambridge/US
  • 19Oncology Clincal Development, Novartis Pharma AG, Basel/CH
  • 20Department Of Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR



Brain metastases, seen in ∼30–50% of NSCLC pts, are associated with poor prognosis. ALK+ NSCLC is sensitive to the ALK inhibitor (ALKi) crizotinib, but resistance invariably occurs, often with progression in new or existing brain metastases. Ceritinib (LDK378), a novel ALKi, is highly active in pts with ALK+ NSCLC and has demonstrated central nervous system activity. Here we report efficacy and safety of ceritinib therapy in the subset of ALK+ NSCLC pts with brain metastases treated in the phase I ASCEND-1 study.


Safety and efficacy of ceritinib 750 mg/day was analyzed based on investigator assessment of adult pts with advanced ALK+ NSCLC and with clinically and neurologically stable brain metastases at study entry.


Of 246 ALK+ NSCLC pts at 750 mg/day, 124 had brain metastases at study entry; 98 had ALKi pretreatment and 26 were ALKi treatment naïve. Pts with brain metastases had a median age of 51.0 years; 85.5% had an ECOG performance status of ≤1. Most pts were either Caucasian (58.1%) or Asian (39.5%); median time from initial NSCLC diagnosis to first ceritinib dose was 20.5 months. Median duration of exposure to ceritinib was 27 weeks. Efficacy is shown below.

Endpointa ALKi-pretreated patients with brain metastases ALKi-naïve patients with brain metastases All NSCLC patients with brain metastases
n = 98 n = 26 n = 124
ORR, n (%)[95% CI] 49 (50.0)[39.7, 60.3] 18 (69.2)[48.2, 85.7] 67 (54.0)[44.9, 63.0]
DOR, median (months) [95% CI] 6.9[4.8, 8.5] NEb[5.5, NE] 7.0[5.5, 9.7]
PFS, median (months) [95% CI] 6.7[4.9, 8.5] 8.3[4.6, NE] 6.9[5.4, 8.4]

NE = Not estimable

aOverall antitumor activity, bDOR rate at 6 months 65.9% [95% CI: 35.4, 84.5]

Brain metastases were identified by investigator assessment as target lesions in 14 pts at baseline using RECIST 1.0 criteria (10 ALKi pretreated, 4 ALKi naïve). Of these, 7 achieved complete or partial responses in the brain (4 ALKi pretreated; 3 ALKi naïve) while 3 had stable disease (all ALKi pretreated). Most common adverse events (all grades; grade 3) in the 124 pts with brain metastases were nausea (82.3%; 4.0%), diarrhea (79.0%; 4.8%), and vomiting (62.9%; 6.5%); no grade 4 observations for these adverse events.


Ceritinib 750 mg/day was efficacious in pts with brain metastases, whether ALKi pretreated or ALKi naïve.


A.T. Shaw: Advisory boards for Novartis, Pfizer, Ariad, Chugai, Genentech; R. Mehra: Spouse is employee of GlaxoSmithKline; Consultancy for Bristol Myers Squibb and Novartis; E. Felip: Advisory boards for Boehringer Ingelheim, Novartis, Roche, Bristol-Myers Squibb, Lilly; L.Q. Chow: Employment by University of Washington; Research grants from Novartis (to institution); Consultancy, travel expenses and advisory board for Novartis; D.R. Camidge: Advisory boards/consultancy/honoraria for Servier, Eli Lilly, Genentech/Roche, Astex, Ariad, ImmunoGen, Clarient, Excelixis, indiPharm, Astellas, Boehringer Ingelheim, Chugai, Clovis, Array Biopharma, AstraZeneca, Aveo, Novartis, Synta, Pfizer; J.F. Vansteenkiste: Speaker for Novartis; S. Sharma: Research grant and consultancy for Novartis; Stock in Salarius Pharmaceuticals, Beta Cat Pharmaceuticals, ConverGene; Board member of TheraTarget and member, VBL Therapeutics IDMC; G.J. Riely: Advisory role for Chugai, Ariad, Daiichi, Tragara, Foundation Medicine, Boehringer Ingelheim, Novartis; Research funding from Pfizer, BMS, Chugai, GSK, Novartis, Infinity; B. Solomon: Honoraria for Novartis, Pfizer, Clovis, AstraZeneca, Roche; Advisory boards for Novartis, Pfizer, Clovis Oncology, AstraZeneca, Roche; J. Wolf: Advisory boards, speakeŕs bureau and research funding, all compensated, by Novartis; M. Thomas: Honoraria for Lilly, BMS, Roche; Consultancy for Lilly, BMS, Roche, Novartis; M. Schuler: Consultant (Compensated): AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer Research grants to institution: Boehringer Ingelheim, Novartis Honoraries for CME lectures: Boehringer Ingelheim, Celgene, GlaxoSmithKline, Lilly, Novartis, Pfizer; G. Liu: Consultancy for Astra Zeneca, Pfizer, Novartis; M. Geraldes: Employment with Novartis; Stock options with Novartis A.L. Boral: Employee of Novartis; A. Yovine: Employment with Novartis; D. Kim: Consultation for Novartis, Pfizer, Lilly; Honorarium from Pfizer, Lilly. All other authors have declared no conflicts of interest.