Publication | Closed Access
Updated result on the 2.5-year follow-up of GC0301/TOP-002: Randomized phase III study of irinotecan plus S-1 (IRI-S) versus S-1 alone as first-line treatment for advanced gastric cancer (AGC)
20
Citations
0
References
2009
Year
Advanced Gastric CancerGastroenterologyPathologyFirst-line TreatmentPharmacotherapyLogistic Analysis2.5-Year Follow-upOncologyGastrointestinal OncologyMetronomic TherapyClinical TrialsDiagnostic SciencesRadiation OncologyMolecular OncologyCancer ResearchHealth SciencesTherapeutic Drug MonitoringClinical TherapeuticPost Protocol TreatmentResponse RateCancer TreatmentPharmacologyMedian Survival TimeAntibioticsClinical PharmacologyMedicinePharmacokinetics
4544 Background: IRI-S had longer in median survival time (MST) than S-1 alone, and was well tolerated in previously untreated AGC, but not statistically significant. Considering 68 patients (pts) were censored, further follow-up was needed to confirm the OS with more precision (Imamura et al. ASCO-GI 2008). We now present updated results of OS and exploratory analysis with the prolonged 2.5 year follow-up data. Methods: Treatments Arm A (oral S-1 80 mg/m 2 /day from Day 1 to 28, q6w), or Arm B (IRI-S; oral S-1 80 mg/m 2 /day from Day 1 to 21 and intravenous irinotecan 80 mg/m 2 on Days 1 and 15, q5w) were continued until disease progression or unacceptable toxicities were observed. The primary endpoint was to compare OS between groups. This updated result was regarded as exploratory position. Results: Although the MST of Arm A was 319 days (95%Cl: 286–395) and of Arm B was 389 days (95%Cl: 324–459), Arm B didn’t show statistically significant superiority to Arm A (log-rank test p=0.54; hazard ratio (HR) =0.93). The 1-year survival was 45.0% in Arm A and 52.0% in Arm B, and the 2-year survival was 22.5% and 18.0%, respectively. Response rate was significantly different (Arm A/B, 26.9%/41.5%; chi-square test p=0.04) in 187 patient evaluated by RECIST criteria. Time to treatment failure was also favored in Arm B (median=138 days) compared to Arm A (111 days; log-rank test p=0.16; HR=0.85). In subset analyses, two groups showed possibility of clinical benefit in Arm B. The HR of diffuse type group was 0.71 (95%Cl: 0.52–0.96), and of PS1, 2 group was 0.63 (95%Cl: 0.42–0.95). As post protocol treatment, 45.6% of Arm A patients received an irinotecan-based regimen, and the MST of them was 496 days (95%Cl: 395–573). Conclusions: IRI-S did not show statistically significant superiority to S-1 alone in OS with this follow-up data. Post protocol treatment, effective treatment after S-1 failure might have affected survival. According to exploratory analyses, IRI-S may have clinical benefit in early-term of treatment, group of the diffuse type and that of PS1, 2. We need more considering predictive factors, because the gastric cancer is heterogeneous adenocarcinoma. [Table: see text]