An open-label, multicentre biomarker-oriented AIO phase II trial of sunitinib for patients with chemo-refractory advanced gastric cancer

• Published in: European journal of cancer (1990) Vol. 47; no. 10; pp. 1511 - 1520
• Main Authors: Moehler, M, Mueller, A, Hartmann, J.T, Ebert, M.P, Al-Batran, S.E, Reimer, P, Weihrauch, M, Lordick, F, Trarbach, T, Biesterfeld, S, Kabisch, M, Wachtlin, D, Galle, P.R
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-07-2011; Elsevier
• Subjects: Adult; Advanced gastric cancer; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomarkers; Biomarkers, Tumor - metabolism; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry - methods; Indoles - therapeutic use; Male; Medical sciences; Middle Aged; Mutation; Objective response; Pharmacology. Drug treatments; Prospective Studies; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyrroles - therapeutic use; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Sunitinib; Treatment Outcome; Tumors; Tyrosine kinase inhibitor; Biomarkers; Sunitinib; Objective response; Tyrosine kinase inhibitor; Advanced gastric cancer; Antineoplastic agent; Human; Treatment resistance; Enzyme; Transferases; Enzyme inhibitor; Biological marker; Malignant tumor; Stomach cancer; Cancerology; Phase II trial; Digestive diseases; Advanced stage; Multikinase inhibitor; Antiangiogenic agent; Protein-tyrosine kinase; Cancer; Gastric disease
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2011.04.006

Abstract Background Sunitinib monotherapy in pretreated patients with advanced gastric cancer (AGC) was investigated. Preplanned analyses of tumour biomarkers on treatment outcome were performed. Patients and methods Patients received sunitinib 50 mg/day for 4 weeks with 2 weeks rest until disease progression or unacceptable toxicity. The primary end-point was objective response rate (ORR). Secondary end-points included progression-free survival (PFS), overall survival (OS) and safety. Results Fifty-two patients were enrolled and treated (safety population, SP). In the intention to treat population ( n = 51); the ORR was 3.9%, median PFS was 1.28 months [95% CI, 1.18–1.90], median OS was 5.81 months [95% CI, 3.48–12.32], the estimated one-year survival rate was 23.7% [95%CI: 12.8–36.5]. In subgroup analyses, tumour VEGF-C expression compared with no expression was associated with significantly shorter median PFS (1.23 versus 2.86 months, logrank p = 0.0119) but there was no difference in tumour control rate ( p = 0.142). In the SP, serious adverse events occurred in 26 patients, leading to 13 deaths, all sunitinib unrelated. Thirty-eight patients died from progressive disease, nine died <60 days after treatment start. Conclusion Sunitinib monotherapy was associated with limited tumour response and good/moderate tolerability in this setting.