Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum

Abstract

Background:Docetaxel is widely used as a chemotherapeutic agent for gastric cancer treatment. A combined regimen with sunitinib demonstrated a synergistic antitumour effect in a preclinical model. The aim of this study was to evaluate the efficacy and safety of this combination in patients with unresectable or metastatic advanced gastric cancer following failure of treatment with a fluoropyrimidine and platinum combination.Methods:This open-label, phase II, randomised trial enrolled patients with unresectable or metastatic gastric cancer. Patients were assigned to either a docetaxel monotherapy arm (D only arm: 60 mg m−2, every 3 weeks) or a combination arm (DS arm: docetaxel+sunitinib 37.5 mg every day). The primary end point of the study was time to progression and the secondary end points were overall response rate, disease control rate, overall survival, and toxicity profile. A pharmacokinetic study was also performed.Results:A total of 107 patients were entered into the study. The TTP was not significantly prolonged in the DS arm when compared with the D only arm (DS vs D only arm: 3.9 months (95% confidence interval (CI) 2.9–4.9) vs 2.6 months (95% CI 1.8–3.5) (P=0.206). The hazard ratio for TTP was 0.77 (95% CI 0.52–1.16). However, the objective response rate was significantly higher in the DS arm (41.1% vs 14.3%, P=0.002). Patients in the DS arm experienced stomatitis, diarrhoea, and hand–foot syndrome more frequently.Conclusion:The addition of sunitinib to docetaxel did not significantly prolong TTP, although it significantly increased response.

Gastric Cancer: New Drugs - New Strategies

“…The time to progression was not significantly prolonged in the docetaxel plus sunitinib arm (table 1). Patients in the docetaxel plus sunitinib arm had more frequently stomatitis, diarrhea and hand-foot syndrome [39]. …”

Gastric cancer: The times they are a-changin’

“…Phase Ⅱ openlabel randomized trial evaluated the combination of sunitinib plus docetaxel vs docetaxel monotherapy in secondline treatment in 107 patients with metastatic gastric cancer. Sunitinib arm was associated with a significantly higher ORR (41.1% vs 14.3%), but there was no significant difference in TTP (3.9 mo vs 2.6 mo) [90] . Sorafenib targets BRAF, VEGF, and PDGFR [91] .…”

A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?

“…For anti-angiogenic agents, this limitation is often due to the lack of validated predictive biomarkers. 26,31,[33][34][35]37,39,52,[60][61][62][63][64] In other cases, in particular for the anti-EGFR agents, even if the prominent role of RAS/RAF mutational status in colon cancer has been widely recognized so far, it is conceivable that this information was unknown at the time of studies design. 27,30,51,[65][66][67] Therefore it is highlighted the need of new trials designed to investigate the relevance of RAS mutation in predicting response to anti-EGFR mAbs, in aGC.…”

“…[22][23][24] Recently, RCTs investigated the efficacy of the targeted therapy alone or in combination with chemotherapy, but results were mostly unsatisfactory. [25][26][27][28][29][30][31][32][33][34][35][36][37][38] While several RCTs demonstrated an improvement in terms of response rate (RR), and progression free survival (PFS) only one study reported a significant increase in terms of OS in a selected subgroup of patients in front-line treatment. 25 In that trial, patients were selected according to HER2 status (resulted to be overexpressed in 16-34% of patients with intestinal type and 2-7% of diffuse aGC), and subsequently treated with trastuzumab plus standard chemotherapy with a significant 2.7 months advantage in OS.…”

“…[25][26][27][28][29][30][31][32][33][34][35][36][37]44,[51][52][53][54][55][56][57][58][59] The TYTAN trial missed data about PFS. One trial missed results about OS.…”