Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine (PCG) and gemcitabine/cisplatin (GC) in patients with locally advanced (LA) or metastatic (M) urothelial cancer without prior systemic therapy; EORTC30987/Intergroup Study

Abstract

LBA5030 Background: GC is a standard alternative to M-VAC for LA/M urothelial cancer (UC) based on comparable efficacy and a more favorable toxicity profile. Based on a phaseII trial, it has been suggested that the PCG triplet might provide improved response and survival. To evaluate the role of paclitaxel when added to GC, a randomized, international study (EORTC30987/Intergroup Study) comparing GC with PCG in LA/M UC was initiated in 2001, with the main endpoint being overall survival (OS). Methods: Chemo naive patients with histologic evidence of LA or M transitional UC, with GFR>60ml/min were eligible. After stratification for institution, PS(WHO 0–1) and presence/absence of metastatic disease, patients were randomized to receive PCG(armA) or GC(armB). PCG treatment included: paclitaxel(P) 80mg/m2 d1&8, cisplatin(C) 70mg/m2 d1 and gemcitabine(G) 1000mg/m2 d1&8, every 21d. GC: C70mg/m2 d1 or 2, G1000mg/m2 d1,8,15 every 28d. To detect an increase in median survival from 14 to 18m(HR=0.778) based on a two sided logrank test at error rates a=0.05 and β=0.20, 498 deaths were required. The planned sample size was of 610 pts. Results: From June 01 to May 04, 627pts (82% primary bladder) were included, (312 PCG, 315 GC). Median age was 61y with 81% males and similar baseline prognostic characteristics on both arms. PS 1 in 47%PCG and 46%GC pts. On PCG 47% had visceral and 83% M; on CG 49%-83% respectively. Overall response rate (RR): 57,1% for PCG (CR15%) and 46,4% for GC (CR10%), p=0.02. Median PFS: 8.4m and 7.7m for PCG and GC, p=0.10. 478 pts have died; the EORTC IDMC has released the study because the required number of events will occur prior to presentation. Median survival is 15.7m for PCG and 12.8m for CG, with no significant difference in OS (p=0.10, HR0.86, CI95% 0.72–1.03, p=0.12 adjusted for risk factors). Both treatments were overall well tolerated, with more thrombopenia and bleeding on GC (12%vs7%) and more febrile neutropenia on PCG (13%vs4%). Conclusions: This large, multicenter, Phase III study shows that PCG provided a better RR when compared with GC in LA/M UC; however the predefined endpoint for PFS and OS improvement was not reached. [Table: see text]