Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib
Por:
Joensuu, H, Blay, JY, Comandone, A, Martin-Broto, J, Fumagalli, E, Grignani, G, Del Muro, XG, Adenis, A, Valverde, C, Pousa, AL, Olivier, B', Italiano, A, Bauer, S, Barone, C, Weiss, C, Crippa, S, Camozzi, M, Castellana, R, Le Cesne, A
Publicada:
1 oct 2017
Resumen:
Background: This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib.
Methods: Patients received oral dovitinib 500 mg day(-1), 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment.
Results: Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2-66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete response+partial response) was 2.6% (1 of 38; 90% CI, 0.1-11.9%), and 5.3% (n = 2; 90% CI, 0.9-15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8-7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n = 7), fatigue (n = 5), vomiting (n = 4), hypertriglyceridaemia (n = 4), and gamma-glutamyltransferase increase (n = 4).
Conclusions: Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib.
Filiaciones:
Joensuu, H:
Helsinki Univ Hosp, Dept Oncol, Haartmaninkatu 4, Helsinki, Finland
Univ Helsinki, Haartmaninkatu 4, Helsinki, Finland
Blay, JY:
Univ Claude Bernard Lyon 1, Ctr Leon Berard, Lyon, France
Comandone, A:
Gradenigo Hosp, Turin, Italy
Martin-Broto, J:
Hosp Univ Virgen del Rocio, Seville, Spain
Fumagalli, E:
Fdn IRCCS Ist Nazl Tumori, Milan, Italy
Grignani, G:
Candiolo Canc Inst FPO, Sarcoma Unit, IRCCS, Candiolo, Italy
Del Muro, XG:
IDIBELL, Inst Catala Oncol, Barcelona, Spain
Adenis, A:
Ctr Oscar Lambret, Lille, France
Valverde, C:
Vall dHebron Univ Hosp, Barcelona, Spain
Pousa, AL:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Olivier, B':
Univ Hosp Robert Debre, Reims, France
Italiano, A:
Inst Bergonie, Comprehens Canc Ctr, Bordeaux, France
Bauer, S:
Univ Duisburg Essen, Sarcoma Ctr, West German Canc Ctr, Essen, Germany
Barone, C:
Univ Cattolica, Univ Hosp A Gemelli, Rome, Italy
Weiss, C:
Novartis Pharma GmbH, Nurnberg, Germany
Crippa, S:
Novartis Farma, Origgio, Italy
Camozzi, M:
Novartis Farma, Origgio, Italy
Castellana, R:
Novartis Farmaceut SA, Barcelona, Spain
Le Cesne, A:
Gustave Roussy, Villejuif, France
Green Published, Hybrid Gold
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