1295P - Efficacy and safety of ceritinib in patients (pts) with advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSC...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Presenter Enriqueta Felip
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors E. Felip1, D. Kim2, R. Mehra3, D.S.W. Tan4, 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. Lui15, A. Santoro16, M. Geraldes17, A.L. Boral18, A. Yovine19, A. Shaw20
  • 1Head Thoracic Oncology Unit, Oncology Department, Vall D'Hebron University Hospital, 08035 - Barcelona/ES
  • 2Department Of Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 3Medical Oncology, Fox Chase Cancer Center, 19111 - Philadelphia/US
  • 4Department Of Medical Oncology, National Cancer Center, 169610 - Singapore/SG
  • 5Department Of Medicine, University of Washington, 98109 - Seattle/US
  • 6Medicine, University of Colorado, Denver/US
  • 7Respiratory Oncology Unit Pulmonology, Universtity 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 - Milano/IT
  • 10Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 11Medical Oncology, Peter MacCallum Cancer Centre, 3002 - East Melbourne/AU
  • 12Dept 1 Of Internal Medicine, Center For Integrated Oncology, University of Cologne, D-50924 - Cologne/DE
  • 13Thoracic Oncology, Thoraxklinik, University of Heidelberg, 69126 - Heidelberg/DE
  • 14Dept. Medical Oncology, West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 15Medical Biophysics, Ontario Cancer Institute, M5P2H7 - Toronto/CA
  • 16Medical Oncology And Hematology, Humanitas Cancer Center, IRCCS, IT-20089 - Rozzano-Milan/IT
  • 17Novartis Pharmaceuticals Corporation, Novartis Pharmaceuticals Corporation, 07936-1080 - East Hanover/US
  • 18Oncology Translational Medicine, Novartis Institutes for BioMedical Research, 02139 - Cambridge/US
  • 19Oncology Clincal Development, Novartis Pharma, 4002 - Basel/CH
  • 20Massachusetts General Hospital Cancer Center, Harvard Medical School, 02114 - Boston/US

Abstract

Aim

ALK+ tumors are sensitive to ALK tyrosine kinase inhibitors such as crizotinib (CRZ) but resistance invariably develops. Ceritinib (LDK378), a novel ALK inhibitor (ALKi), is more potent than CRZ in vitro and is effective in CRZ-resistant disease. Updated data from ASCEND-1 (NCT01283516) are presented, focused on pts receiving ceritinib at the recommended 750 mg/day dose and with longer follow-up.

Methods

Investigator assessment of efficacy is presented for pts with ALK+ NSCLC receiving ≥1 dose of ceritinib at 750 mg/day prior to 31 Oct 2013. Results with additional follow-up will be presented.

Results

246 pts with ALK+ NSCLC had 7 months median duration of follow up. Of these, 230 (93%) had received prior antineoplastic therapy, 166 (67%) with ≥2 prior regimens.163 (66%) had received prior ALKi, all of whom had received CRZ; of these, 91% had progressive disease during prior ALKi therapy and 78% had received ALKi as last prior therapy. Efficacy is shown below.

Endpoint All NSCLCn = 246 ALKi-pretreatedn = 163 ALKi-naïven = 83
ORR, n (%)[95% CI] 144 (58.5)[52.1, 64.8] 89 (54.6)[46.6, 62.4] 55 (66.3)[55.1, 76.3]
DOR, median (months)[95% CI] 9.7 [7.0, 11.4] 7.4 [5.4, 10.1] NEa [9.6, NE]
Time to first response, median (weeks) [min, max] 6.1 wks[3.0, 24.1] 6.1 wks[4.6, 24.1] 6.1 wks[3.0, 24.1]
PFS, median (months)[95% CI] 8.2 [6.7, 10.1] 6.9 [5.4, 8.4] NEb [8.3, NE]

aDOR rate at 12 mos 65.2% [95% CI: 46.4, 78.8]

bPFS rate at 12 mos 61.3% [95% CI: 47.7, 72.3]

NE = Not estimable.

Discontinuation of treatment due to adverse event (AE) occurred in 24 (10%) pts with NSCLC; 17 (10%) ALKi-pretreated pts and 7 (8%) ALKi-naïve pts. Among all 255 pts receiving ceritinib 750 mg/day, 99 (39%) and 51 (20%) required 1 and >1 ceritinib dose reduction, respectively. The most common AEs of any grade (>50%) were diarrhea (86%), nausea (80%), vomiting (60%), abdominal pain (54%), fatigue (52%). Most common lab abnormalities of any grade (>50%) were decreased hemoglobin (84%), increased ALT (80%), increased AST (75%), increased creatinine (58%). Most common Grade 3/4 lab abnormalities (>10%) were increased ALT (27%), increased AST (13%), increased glucose (13%). One treatment-related death (interstitial lung disease) was reported.

Conclusions

Ceritinib 750 mg/day shows potent anti-tumor activity in ALK+ NSCLC pts regardless of prior ALKi treatment status. Discontinuation due to toxicity was uncommon.

Disclosure

E. Felip: Advisory board: BI, Novartis, Roche, BMS, Lilly; D. Kim: Consultation for Novartis, Pfizer, Lilly; Honorarium from Pfizer, Lilly; R. Mehra: Spouse is an employee of GSK, consulting to Bristol-Myers Squibb and Novartis; L.Q. Chow: Employee: University of Washington; Research grant and research support, consultant, travel expenses and advisory board: 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, Consultant: Novartis. Stock: Salarius Pharma, Beta Cat Pharma, ConverGene. Leadership: Board member, TheraTarget and Member, VLB Therapeutics IDMC; B. Solomon: Honoraria/Ad board: Novartis, Pfizer, Clovis, Clovis oncology, AZ, Roche; J. Wolf: Employee of University Hospital of Cologne. Ad boards, speakers bureau and research funding: AZ, Novartis, Roche, Pfizer, BI, BMS, Clovis. Research support: Novartis, Roche, BI; M. Thomas: Honoraria: Lilly, BMS, Roche. Consultant: Lilly, BMS, Roche, Novartis ; M. Schuler: Consultant: AZ, BI, Novartis, Pfizer. Research grants to institution: BI, Novartis. Honoraries for CME lectures: BI, Celgine, GSK, Lilly, Novartis, Pfizer; G. Lui: Consultant: AZ, Pfizer, Novartis; M. Geraldes: Margarida Geraldes is an employee of Novartis and is a stock owner; A.L. Boral: Antony L Boral is an employee of Novartis; A. Yovine: Alejandro Yovine is an employee of Novartis and is a stock owner; A.T. Shaw: Advisory board: Novartis, Pfizer, Ariad, Chugai, Genentech. All other authors have declared no conflicts of interest.