Nilotinib in advanced GIST : a retrospective analysis of nilotinib in compassionate use

Details

Serval ID
serval:BIB_F488A93301E1
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Nilotinib in advanced GIST : a retrospective analysis of nilotinib in compassionate use
Title of the conference
30th Annual meeting of the ASCO
Author(s)
Montemurro M., Schöffski P., Reichardt P., Gelderblom H., Joensuu H., Schütte J., Wendtner C.M., Hartmann J.T., Elsig V., Leyvraz S.
Address
Chicago, Illinois, May 30-June 3, 2008
ISBN
0732-183X
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
26
Series
Journal of Clinical Oncology
Pages
10523
Language
english
Notes
Background: Tyrosine kinase inhibitors (TKI) have considerably improved outcome of advanced GIST. First-line imatinib treatment achieves an excellent mOS of 5 years, yet, a mPFS of approximately 2 years with first-line imatinib and 24 weeks with second-line sunitinib calls for treatment alternatives. Nilotinib is a second-generation TKI with at least similar inhibitory activity as imatinib, but reaching 7-10 fold higher intracellular concentrations. A Phase I study has shown that nilotinib monotherapy has clinical activity in GIST. Methods: Patients (pts) failing all available therapeutic options had access to nilotinib on a compassionate use (CU) programm. Nilotinib starting dose was 400 mg bid, with an allowed dose reduction to 400 mg qd for toxicity. 94 pts were approved for nilotinib CU in 10 European countries. We herein present retrospective data of 36 pts from 5 European countries treated in 8 centers. Results: Median age at nilotinib treatment start was 59 years (median; range 24-79 y), and 70% of pts were male. Most pts had metastatic disease of gastric origin at initial diagnosis. KIT exon 11 mutations were most frequent. The median number of surgical resections was 1 (range 0-8). All pts had failed both imatinib and sunitinib before nilotinib, and 8% had also received additional investigational treatments. Nilotinib was well tolerated, as only 14% discontinued nilotinib due to toxicity. Median follow-up is 156 days (range 15-765 d). Nilotinib treatment duration is 60 days (median; range 3-727 d) and one third of pts were treated for longer than 3 months. Partial remission with nilotinib treatment was seen in 6% of pts. Median OS was 211 days (Kaplan-Meier). Conclusions: This is the largest series assessing efficacy of nilotinib for imatinib- and sunitinib-refractory GIST reported yet. Nilotinib displays significant clinical activity in this heavily pretreated group of pts. One third of pts have disease control on nilotinib for longer than three months. These results warrant further investigation of nilotinib in GIST, including its use in first or second-line treatment. Patient and data collection is ongoing, updated results will be presented at ASCO 2008.
Create date
17/03/2009 15:43
Last modification date
20/08/2019 16:21
Usage data