GemOx (Gemcitabine + Oxaliplatin) versus Gem (Gemcitabine) in non resectable pancreatic adenocarcinoma : final results of the GERCOR /GISCAD Intergroup Phase III
Christophe Louvet, Roberto Labianca, Pascal Hammel, Gérard Lledo, Filippo de Braud, Thierry André, Maurizio Cantore, Michel Ducreux, Alberto Zaniboni, Aimery de Gramont.
Background: The combination of gemcitabine 1 g/m² as a 100 min infusion (10 mg/m²/mn) D1 and oxaliplatin 100 mg/m² in 2h infusion D2 (GemOx) every two weeks showed interesting results in a multicenter phase II study (Louvet et al, JCO 2002) and was thus further explored in a phase III randomised study. Methods: Patients were stratified according to center, performance status and type of disease (locally-advanced (LA) versus metastatic (M)) and were randomly assigned to GemOx or standard treatment with gemcitabine alone (1 g/m² in a 30 min infusion weekly). 300 patients were needed to demonstrate an absolute improvement of 20% in 8-month survival (30% to 50%).
Results: 326 patients have been enrolled; 13 were non eligible, 156 were allocated to Gem arm and 157 to GemOx. Preliminary results presented last year (Louvet, ASCO 2003) were actualized and confirm a significant improvement for the GemOx arm in response rate (28.7% vs 16.7%, p = 0.02), median progression free survival (5.5 months vs 3.7, p = 0.04), and clinical benefit (38.9% vs 29.2%, p = 0.05), with a good tolerability of the GemOx combination. Final analysis (March 04) has shown median overall survival of 7.1 months (Gem) and of 9.0 months (Gemox), respectively (p = 0.13, HR 1.20 [.95 – 1.54]). The 8-month survival probability was 45% in the Gem arm and 56% in the Gemox arm. For LA pts (30% of total enrolled), median survivals were identical (10.3 months) in both arm, while for M pts (70%), median survival was 6.7 months (Gem) arm and 8.5 months (Gemox), respectively (p = 0.17; HR 1.21 [.91 – 1.63]. A second-line chemotherapy was administered in 53.4% of the Gem pts (mainly platin-based) and in 52.3% of the Gemox pts (miscellaneous).
Conclusion: Gemox achieved significantly better results than Gem in terms of RR, clinical benefit and PFS, but the difference did not reach the significant level for OS.