This study presents a re-analyses of the efficacy and safety data from the ML17032 trial to confirm the non-inferiority and test the potential superiority of a capecitabine (Xeloda®)/ cisplatin (XP) combination over a 5-fluorouracil (5-FU)/cisplatin (FP) regimen as first-line treatment for advanced gastric cancer (AGC) in Chinese patients.
In this open label phase III trial, patients with advanced gastric cancer (Stage IIIA-IV) with or without metastases were randomized 1:1 to receive Cisplatin (80mg/m2/day IV day 1) with either Capecitabine (1000mg/m2/day PO BID, days1-14) (XP) or 5-FU (800mg/m2/day continuous IV days 1-5) (FP) every 3 weeks. The primary objective was to confirm the non -inferiority of XP over FP for progression free survival (PFS).
A total of 126 Chinese patients (XP-62, FP-64; 75.4% male, median age 55.5 years) were enrolled as the intent to treat population. The per-protocol population consisting of 105 patients (XP-51, FP-54; 64.7% male) served as the primary analysis group for establishing non-inferiority. Median PFS in the XP and FP groups was 7.2 and 4.5 months respectively. The primary efficacy endpoint of PFS was met with an adjusted hazard Ratio (HR) of 0.52 (95% Confidence interval [CI]: [0.32-0.83], p = 0.006). Unadjusted HR for PFS in ITT population was 0.63 (95% CI: [0.42-0.94], p = 0.022). Among secondary efficacy endpoints OS (adjusted HR 0.61 [0.37-1.01], p = 0.053) and TTF (HR 0.54, [0.35, 0.84], p = 0.006) demonstrated a trend towards superiority of XP over FP. Drug exposure was similar among 2 groups in the safety population (XP-58, FP-62, 68.3% male). The most frequent drug related Grade 3/4 AEs were neutropenia (XP-20.7%; FP-17.7%) and gastrointestinal disorders (XP-19.0%; FP-19.4%). The overall incidence of grade 3/4 AEs (XP-43.1%; FP-46.8%), SAEs (XP-1.7%; FP-3.2%), and AEs related to treatment discontinuation (XP-10.3%; FP-16.1%) were comparable among the 2 groups.
XP may demonstrate superiority for PFS and TTF compared to FP in the first-line treatment of Chinese patients with AGC and had a similar safety profile to FP.
Clinical trial identification
Legal entity responsible for the study
This study was sponsored by Shanghai Roche Pharmaceuticals Ltd, China (ML 17032)
Y. Gao: Employee of Shanghai Roche Pharmaceuticals Ltd. All other authors have declared no conflicts of interest.