LBA46 - Phase 2 trial to evaluate the efficacy and safety of dovitinib in patients (pts) with gastrointestinal stromal tumor (GIST) refractory and/or intol...

Date 27 September 2014
Event ESMO 2014
Session Sarcoma
Topics Anti-Cancer Agents & Biologic Therapy
Presenter Heikki Joensuu
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors H. Joensuu1, J. Blay2, A. Comandone3, J. Martin Broto4, E. Fumagalli5, G..E. Grignani6, X. Garcia Del Muro7, A. Adenis8, C. Valverde Morales9, A. Lopez Pousa10, O. Bouché11, B. Bui12, S. Bauer13, C. Barone14, C. Weiss15, S. Crippa16, M. Camozzi17, R. Castellana17, A. Le Cesne18
  • 1Oncology, Helsinki Univerity Central Hospital (HUCH), FI-00290 - Helsinki/FI
  • 2University Claude Bernard Lyon I, Centre Léon Bérard, 69008 - Lyon/FR
  • 3Oncologia Medica, Ospedale Gradenigo, IT-10153 - Torino/IT
  • 4Sarcoma And Melanoma Units, Son Espases Hospital, Palma de Mallorca/ES
  • 5Adult Mesenchymal Tumour Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 20133 - Milan/IT
  • 6Medical Oncology, IRCC - Fondazione Piemontese per la Ricerca sul Cancro Onlus, Candiolo/IT
  • 7Medical Oncology, Instituto Catalan d'Oncologia, 08907 - L'Hospitalet de Llobregat/ES
  • 8Service D’oncologie Médicale, Centre Oscar Lambret, 59020 - Lille/FR
  • 9Oncologia Médica, Vall Hebron Univerity Hospital, Barcelona/ES
  • 10Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08041 - Barcelona/ES
  • 11Service D'hépato-gastroentérologie Et De Cancérologie Digestive, Centre Hospitalier Universitaire Robert Debré, Reims/FR
  • 12Medical Oncology, Institute Bergoni, FR-33076 - Bordeaux CEDEX/FR
  • 13Innere Medizin / Tumorforschung, University Hospital Essen Westdeutsches Tumorzentrum, Essen/DE
  • 14Oncologia Medica, Università Cattolica del Sacro Cuore, 00168 - Roma/IT
  • 15Oncology, Novartis Pharma GmbH, Nuernberg/DE
  • 16Ore Rare Disease Franchise, Novartis Farma S.p.A., Origgio/IT
  • 17Oncology Region Europe, Novartis Farma S.p.A., Origgio/IT
  • 18Medical Oncology, Institut Gustave Roussy, 94805 - VILLEJUIF/FR




Sunitinib is approved for advanced GIST resistant/refractory to IM; however, disease control rate (DCR) at 12 wk was only ≈ 40%. Thus, novel therapeutic second-line strategies are needed to improve outcomes. Dovitinib inhibits several tyrosine kinases (eg, FGFR, VEGFR, PDGFRß, KIT). DOVIGIST (NCT01478373) is a multicenter, single-arm study to evaluate the efficacy and safety of second-line dovitinib in GIST.


Eligible pts (≥ 18 y) had histologically confirmed GIST; pts had advanced/metastatic GIST refractory/intolerant to IM ≥ 400 mg/day or recurrent GIST after adjuvant IM. All pts had ≥ 1 measurable lesion at baseline. Prior tyrosine kinase inhibitors other than IM were not allowed. Pts received dovitinib 500 mg/day (5 days on/2 days off) until progressive disease (PD), unacceptable toxicity, death, or discontinuation. The primary endpoint was DCR (per RECIST 1.1) at 12 wk. Based on prior trials, DCR ≥45% was deemed clinically meaningful. Key secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and safety.


Of 39 pts who received ≥1 dose of dovitinib, 1 had unconfirmed GIST histology; thus, the efficacy analysis included 38 pts (median age, 60 y). The median time from diagnosis to first dose of dovitinib was 46.3 mo; 81.6% had PD on IM, 13.2% discontinued IM due to intolerance, and 5.2% had intolerance and PD. The most common grade 3/4 dovitinib-related adverse events (AEs) were fatigue (12.8%), diarrhea, vomiting, and hypertriglyceridemia (7.7% each); 21.1% discontinued due to AEs. One pt died of a heart attack (suspected drug related). The median PFS was 20.1 wk (90% CI, 12.3-32.1). DCR at 12 wk was 52.6% (Table).


DOVIGIST met its primary endpoint. The DCR of 52.6% compares favorably with that of other second-line treatments. Dovitinib had promising efficacy and a manageable safety profile, warranting further studies in GIST.

Best Response at 12 Wk, n = 38 n % 90% CI
Partial response (PR) 1 2.6
Stable disease (SD) 19 50.0
PD 5 13.2
Unknowna 13 34.2
ORR (≥ PR) 1 2.6 0.1-11.9
DCR (≥ SD) 20 52.6 38.2-66.7

a Not all baseline lesions evaluated during follow-up; no PD detected ≤12 wk on dovitinib.


H. Joensuu: The Clinical Research Institute of Helsinki University Hospital has received financial support from Novartis and Bayer AG because HJ participated in advisory group meetings or speaking events; J-Y. Blay: Received research support and honoraria from Novartis, GSK, Roche, Pharmamar, Bayer, MSD, JNJ; E. Fumagalli: Founds for studies and research activities: Amgen Dompè, Bayer, Glaxo SK, Merck SD, Novartis, Pfizer, PharmaMar, Sanofi-Aventis, ImClone, Infinity, Janssen Cilag, Lilly, Molmed, Merck SD, Schering Plough Travel for medical meetings: Novartis; G.E. Grignani: Received travel reimbursement from PharmaMar. Expert opinion for Bayer and Glaxo-Welcome; O. Bouché: Received research support and honoraria from Novartis; S. Bauer: received honoraria by Novartis, Pfizer, Bayer and have received a research grant by Novartis (for a clinical trial). Advisory board for Pfizer; C. Barone: Received honoraria as a speaker and chairman; C. Weiss, S. Crippa, M. Camozzi and R. Castellana: Novartis employee; A. Le Cesne: Received honoraria from GSK, Novartis, Pharmamar and Pfizer for advisory board. All other authors have declared no conflicts of interest.