IS3-2 - A Phase 2 Trial of Ixabepilone in Asian Patients with Advanced Gastric Cancer Previously Treated with Fluoropyrimidine-Based Chemotherapy

Abstract

ABSTRACT Background The highest rates of gastric cancer occur in Eastern Asia. Fluoropyrimidine-based therapy is used initially in unresectable and metastatic disease, following progression, 60–70% of patients in Asian countries subsequently receive second-line chemotherapy. However, there is no standard treatment in this setting. Ixabepilone, an epothilone B analog, is a non-taxane microtubule-stabilizing agent with clinical anti-tumor activity across multiple tumor types. We evaluated the efficacy and safety of single-agent ixabepilone as a second-line chemotherapy in Asian patients. Methods Asian patients with unresectable or metastatic gastric adenocarcinoma who had failed previous fluoropyrimidine-based chemotherapy received ixabepilone 40 mg/m2 by 3-hour intravenous infusion every 3 weeks. The primary end point was objective response rate (ORR). In this study, an ORR ≤8% was not of clinical interest, and an ORR ≥20% was of strong clinical interest. The test had 80% power to reject the null hypothesis at a significance level of 5% if the true ORR is 20%. Results This phase II was conducted at 9 sites in the Asian-Pacific region including Japan, Korea, Taiwan, Hong Kong and Singapore from November 2009 to June 2011. Fifty-two patients were treated (65.4% male; median age: 56.5 years). Ixabepilone was administered for a median of 3.5 courses (range: 1–10). Of the 45 patients who received at least two courses. The ORR was 15.4% (95% CI: 6.9–28.1), with 8 patients achieving partial responses for a median duration of 3.1 months (95% CI: 2.6–4.1 months). Twenty-six patients (50.0%) had stable disease, and therefore the disease control rate was 65.4% (95% CI: 50.9–78.0). Median progression-free survival was 2.8 months (95% CI: 2.1–3.5 months). The most common grade 3 non-hematological toxic effects were fatigue (9.6%), decreased appetite (7.7%), and peripheral sensory neuropathy (5.8%). Grade 3/4 neutropenia occurred in 46.2% of patients, with febrile neutropenia in 7.7%. There was no treatment-related death. Conclusion Ixabepilone showed a modest efficacy in Asian patients with advanced gastric cancer following prior fluoropyrimidine-based therapy, and has a predictable and manageable safety profile consistent with that seen in other tumor types.