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.
  
  
  CONCLUSIONS
  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.
authors: Institut Bergonié, Bordeaux, France. italiano@bergonie.org
authors: Antoine
authors: A
authors: Italiano
authors: Angela
authors: A
authors: Cioffi
authors: Paola
authors: P
authors: Coco
authors: Robert G
authors: RG
authors: Maki
authors: Patrick
authors: P
authors: Schöffski
authors: Piotr
authors: P
authors: Rutkowski
authors: Axel
authors: A
authors: Le Cesne
authors: Florence
authors: F
authors: Duffaud
authors: Antoine
authors: A
authors: Adenis
authors: Nicolas
authors: N
authors: Isambert
authors: Emmanuelle
authors: E
authors: Bompas
authors: Jean-Yves
authors: JY
authors: Blay
authors: Paolo
authors: P
authors: Casali
authors: Mary Louise
authors: ML
authors: Keohan
authors: Maud
authors: M
authors: Toulmonde
authors: Cristina R
authors: CR
authors: Antonescu
authors: Maria
authors: M
authors: Debiec-Rychter
authors: Jean-Michel
authors: JM
authors: Coindre
authors: Binh
authors: B
authors: Bui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D001557:Benzenesulfonates / Q000008:administration & dosage*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010879:Piperazines / Q000008:administration & dosage; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011725:Pyridines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate; D055815:Young Adult
chemical_list: D001549:Benzamides; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D012709:Serum Albumin; D009536:Niacinamide; D000068877:Imatinib Mesylate; D000077157:Sorafenib; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C498826:nilotinib; D000077210:Sunitinib