Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis

被引:16
作者
Vincenzi, Bruno [1 ]
Nannini, Margherita [2 ]
Fumagalli, Elena [3 ]
Bronte, Giuseppe [4 ]
Frezza, Anna Maria [1 ]
De Lisi, Delia [1 ]
Ceruso, Mariella Spalato [1 ]
Santini, Daniele [1 ]
Badalamenti, Giuseppe [4 ]
Pantaleo, Maria Abbondanza [2 ]
Russo, Antonio [4 ]
Dei Tos, AngeloPaolo [5 ]
Casali, Paolo [3 ]
Tonini, Giuseppe [1 ]
机构
[1] Univ Campus Biomed, Dept Oncol, Rome, Italy
[2] Univ Bologna, St Orsola Malpighi Hosp, Dept Specialized Expt & Diagnost Med, Bologna, Italy
[3] Fdn IRCCS Ist Nazl Tumori, Adult Mesenchymal Tumor Med Oncol Unit, Milan, Italy
[4] Univ Palermo, Dept Surg Oncol & Oral Sci, Sect Med Oncol, Palermo, Italy
[5] Gen Hosp Treviso, Dept Pathol & Oncol, Treviso, Italy
关键词
imatinib; sunitinib; second line; GIST; exon; 11; GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE; C-KIT; MUTATIONS; EFFICACY; SAFETY; MULTICENTER; RESISTANCE; TRIAL;
D O I
10.18632/oncotarget.5136
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line. All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits. 64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5 months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). No difference was found in patients treated with sunitinib (P = 0.370). A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Deletions in exon 11 seemed to be correlated with worse outcome in patients receiving imatinib-based second line.
引用
收藏
页码:69412 / 69419
页数:8
相关论文
共 22 条
[1]   Autoinhibition of the Kit receptor tyrosine kinase by the cytosolic juxtamembrane region [J].
Chang, PM ;
Ilangumaran, S ;
La Rose, J ;
Chakrabartty, A ;
Rottapel, R .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (09) :3067-3078
[2]   KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours [J].
Debiec-Rychter, Maria ;
Sciot, Raf ;
Le Cesne, Axel ;
Schlemmer, Marcus ;
Hohenberger, Peter ;
van Oosterom, Allan T. ;
Blay, Jean-Yves ;
Leyvraz, Serge ;
Stul, Michel ;
Casali, Paolo G. ;
Zalcberg, John ;
Verweij, Jaap ;
Van Glabbeke, Martine ;
Hagemeijer, Anne ;
Judson, Ian .
EUROPEAN JOURNAL OF CANCER, 2006, 42 (08) :1093-1103
[3]   Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors [J].
Demetri, GD ;
von Mehren, M ;
Blanke, CD ;
Van den Abbeele, AD ;
Eisenberg, B ;
Roberts, PJ ;
Heinrich, MC ;
Tuveson, DA ;
Singer, S ;
Janicek, M ;
Fletcher, JA ;
Silverman, SG ;
Silberman, SL ;
Capdeville, R ;
Kiese, B ;
Peng, B ;
Dimitrijevic, S ;
Druker, BJ ;
Corless, C ;
Fletcher, CDM ;
Joensuu, H .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (07) :472-480
[4]   Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial [J].
Demetri, George D. ;
van Oosterom, Allan T. ;
Garrett, Christopher R. ;
Blackstein, Martin E. ;
Shah, Manisha H. ;
Verweij, Jaap ;
McArthur, Grant ;
Judson, Ian R. ;
Heinrich, Michael C. ;
Morgan, Jeffrey A. ;
Desai, Jayesh ;
D Fletcher, Christopher ;
George, Suzanne ;
Bello, Carlo L. ;
Huang, Xin ;
Baum, Charles M. ;
Casali, Paolo G. .
LANCET, 2006, 368 (9544) :1329-1338
[5]   Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial [J].
Demetri, George D. ;
Reichardt, Peter ;
Kang, Yoon-Koo ;
Blay, Jean-Yves ;
Rutkowski, Piotr ;
Gelderblom, Hans ;
Hohenberger, Peter ;
Leahy, Michael ;
von Mehren, Margaret ;
Joensuu, Heikki ;
Badalamenti, Giuseppe ;
Blackstein, Martin ;
Le Cesne, Axel ;
Schoffski, Patrick ;
Maki, Robert G. ;
Bauer, Sebastian ;
Binh Bui Nguyen ;
Xu, Jianming ;
Nishida, Toshirou ;
Chung, John ;
Kappeler, Christian ;
Kuss, Iris ;
Laurent, Dirk ;
Casali, Paolo G. .
LANCET, 2013, 381 (9863) :295-302
[6]   Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer [J].
Faivre, S ;
Delbaldo, C ;
Vera, K ;
Robert, C ;
Lozahic, S ;
Lassau, N ;
Bello, C ;
Deprimo, S ;
Brega, A ;
Massimini, G ;
Armand, JP ;
Scigalla, P ;
Raymond, E .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (01) :25-35
[7]   Secondary mutations of c-KIT contribute to acquired resistance to imatinib and decrease efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors [J].
Gao, Jing ;
Tian, Ye ;
Li, Jian ;
Sun, Naiping ;
Yuan, Jiajia ;
Shen, Lin .
MEDICAL ONCOLOGY, 2013, 30 (02)
[8]   Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure [J].
George, S. ;
Blay, J. Y. ;
Casali, P. G. ;
Le Cesne, A. ;
Stephenson, P. ;
DePrimo, S. E. ;
Harmon, C. S. ;
Law, C. N. J. ;
Morgan, J. A. ;
Ray-Coquard, I. ;
Tassell, V. ;
Cohen, D. P. ;
Demetri, G. D. .
EUROPEAN JOURNAL OF CANCER, 2009, 45 (11) :1959-1968
[9]   PDGFRA activating mutations in gastrointestinal stromal tumors [J].
Heinrich, MC ;
Corless, CL ;
Duensing, A ;
McGreevey, L ;
Chen, CJ ;
Joseph, N ;
Singer, S ;
Griffith, DJ ;
Haley, A ;
Town, A ;
Demetri, GD ;
Fletcher, CDM ;
Fletcher, JA .
SCIENCE, 2003, 299 (5607) :708-710
[10]   Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor [J].
Heinrich, MC ;
Corless, CL ;
Demetri, GD ;
Blanke, CD ;
von Mehren, M ;
Joensuu, H ;
McGreevey, LS ;
Chen, CJ ;
Van den Abbeele, AD ;
Druker, BJ ;
Kiese, B ;
Eisenberg, B ;
Roberts, PJ ;
Singer, S ;
Fletcher, CDM ;
Silberman, S ;
Dimitrijevic, S ;
Fletcher, JA .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (23) :4342-4349