title: Hypertension as a potential biomarker of efficacy in patients with gastrointestinal stromal tumor treated with sunitinib.
abstract: BACKGROUND
  Reliable biomarkers of sunitinib response in gastrointestinal stromal tumor (GIST) are lacking. Hypertension (HTN), an on-target class effect of vascular endothelial growth factor signaling-pathway inhibitors, has been shown to correlate with clinical outcome in advanced renal cell carcinoma treated with sunitinib.
  
  
  METHODS
  This retrospective analysis examined correlations between sunitinib-associated HTN and antitumor efficacy (N = 319) and safety (N = 1565) across three advanced GIST studies. Blood pressure (BP) was measured on days 1 and 28 of each treatment cycle at a minimum. Time-to-event endpoints were estimated using Kaplan-Meier methods, and patient subgroups with and without HTN (maximum systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) were compared using Cox proportional hazards models. Landmark analyses evaluated associations between early HTN and efficacy endpoints. Adverse events (AEs) were compared between groups.
  
  
  RESULTS
  Sunitinib-associated HTN correlated with improved objective response rates, time to tumor progression, progression-free survival, and overall survival. Almost all benefits remained significant in multivariate and landmark analyses. Overall incidences of HTN-related AEs were low and similar between groups; incidences of cardiovascular AEs were somewhat higher in patients with HTN.
  
  
  CONCLUSIONS
  Sunitinib-associated HTN appeared to correlate with improved clinical outcomes in GIST, while incidences of HTN-associated AEs were generally low and manageable.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA. Electronic address: suzanne_george@dfci.harvard.edu.
authors.forename: S
authors.initials: S
authors.lastname: George
authors.affiliation: Department of Internal Medicine, HELIOS Klinikum Bad Saarow, Bad Saarow, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Reichardt
authors.affiliation: Pfizer Oncology, New York, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lechner
authors.affiliation: Pfizer Oncology, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Pfizer Oncology, La Jolla, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Cohen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Ludwig Center at Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Demetri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001794:Blood Pressure / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D000068877:Imatinib Mesylate; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction; D000077210:Sunitinib; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D042442:Vascular Endothelial Growth Factors; D000068877:Imatinib Mesylate; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib