Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib Journal Article

  

Authors:	Italiano, A.; Cioffi, A.; Coco, P.; Maki, R. G.; Schöffski, P.; Rutkowski, P.; Le Cesne, A.; Duffaud, F.; Adenis, A.; Isambert, N.; Bompas, E.; Blay, J. Y.; Casali, P.; Keohan, M. L.; Toulmonde, M.; Antonescu, C. R.; Debiec-Rychter, M.; Coindre, J. M.; Bui, B.
Article Title:	Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib
Abstract:	Background. Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd-line sunitinib are limited. Methods. Medical records of 223 imatinib-resistant and sunitinib-resistant GIST who were treated in 11 major referral centers were reviewed. Results. The three most frequent drugs used in the 3rd-line setting were: nilotinib n = 67 (29.5%), sorafenib n = 55 (24.5%), and imatinib n = 40 (17.5%). There were 18 patients (8%) who received best supportive care (BSC) only. The median progression-free survival (PFS) and overall survival (OS) on 3rd-line treatment were 3.6 months [95% confidence interval (95% CI), 3.1-4.1] and 9.2 months (95% CI, 7.5-10.9), respectively. Multivariate analysis showed that, in the 3rd-line setting, albumin level and KIT/PDGFRA mutational status were significantly associated with PFS, whereas performance status and albumin level were associated with OS. After adjustment for prognostic factors, nilotinib and sorafenib provided the best PFS and OS. Rechallenge with imatinib was also associated with improved OS in comparison with BSC. Conclusion. In the 3rd-line setting, rechallenge with imatinib provided limited clinical benefit but was superior to BSC. Sorafenib and nilotinib have significant clinical activity in imatinib-resistant and sunitinib-resistant GIST and may represent an alternative for rechallenge with imatinib. © Society of Surgical Oncology 2011.
Keywords:	adult; cancer survival; aged; aged, 80 and over; disease-free survival; middle aged; survival rate; retrospective studies; young adult; gene mutation; major clinical study; overall survival; mutation; sorafenib; bevacizumab; doxorubicin; sunitinib; drug efficacy; benzenesulfonates; liver neoplasms; pyridines; gemcitabine; gastrointestinal stromal tumor; imatinib; gastrointestinal stromal tumors; proto-oncogene proteins c-kit; receptor, platelet-derived growth factor alpha; dacarbazine; metastasis; progression free survival; etoposide; antineoplastic combined chemotherapy protocols; risk factors; cyclophosphamide; drug resistance, neoplasm; pyrimidines; gastrointestinal neoplasms; patient care; multivariate analysis; piperazines; nilotinib; indoles; pyrroles; rapamycin; serum albumin
Journal Title:	Annals of Surgical Oncology
Volume:	19
Issue:	5
ISSN:	1068-9265
Publisher:	Springer
Date Published:	2012-05-01
Start Page:	1551
End Page:	1559
Language:	English
DOI:	10.1245/s10434-011-2120-6
PROVIDER:	scopus
PUBMED:	22065192
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84862556696&partnerID=40&md5=3609bc8fb1a0777626c1277a33322cda
Notes:	--- - "Export Date: 2 July 2012" - "CODEN: ASONF" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/29121