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

Italiano, A., Cioffi, A., Coco, P., Maki, R. G., Schoffski, 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. (May 2012) Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib. Ann Surg Oncol, 19 (5). pp. 1551-9. ISSN 1534-4681 (Electronic)1068-9265 (Linking)

DOI: 10.1245/s10434-011-2120-6


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.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Benzamides Benzenesulfonates/*administration & dosage Disease-Free Survival *Drug Resistance, Neoplasm Female Gastrointestinal Neoplasms/*drug therapy/genetics/metabolism/mortality Gastrointestinal Stromal Tumors/*drug therapy/genetics/metabolism/mortality/secondary Humans Imatinib Mesylate Indoles/administration & dosage Liver Neoplasms/secondary Male Middle Aged Multivariate Analysis Mutation Niacinamide/analogs & derivatives Phenylurea Compounds Piperazines/administration & dosage Prognosis Proto-Oncogene Proteins c-kit/genetics Pyridines/*administration & dosage Pyrimidines/*administration & dosage Pyrroles/administration & dosage Receptor, Platelet-Derived Growth Factor alpha/genetics Retrospective Studies Risk Factors Serum Albumin/metabolism Survival Rate Young Adult
Subjects: diseases & disorders > cancer > drugs and therapies > chemoresistance
diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > gastrointestinal stromal tumors
diseases & disorders > cancer > metastasis
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: May 2012
Date Deposited: 20 Oct 2016 20:43
Last Modified: 20 Oct 2016 20:43
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