Gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer, but a phase I/II study suggested paclitaxel plus GC (PGC) may have greater antitumor activity and could possibly improve survival. EORTC trial 30987 was a randomized phase III study designed to compare PGC with GC in patients with locally advanced or metastatic urothelial carcinoma.
626 patients were randomized, 312 to PGC and 314 to GC. The median follow-up was 4.6 years.
Median overall survival, the primary endpoint, was 15.8 months for patients treated with PGC and 12.7 months for patients treated with GC (hazard ratio [HR] = 0.85; P = 0.075). Overall survival in the subgroup of all eligible patients was significantly longer for those treated with PGC (3.2 months; HR = 0.82; P = 0.03), as was the case in patients with bladder primary tumors.
Progression-free survival was not significantly longer on PGC (HR = 0.87; P = 0.11). Overall response rate was 55.5% for patients treated with PGC and 43.6% for patients treated with GC (P = 0.0031).
Both treatments were well tolerated, but patients treated with GC experienced more thrombocytopenia and bleeding, 11.4%, than did those treated with PGC, 6.8% (P = 0.05), and patients treated with PGC experienced more febrile neutropenia, 13.2%, than did those treated with GC, 4.3% (P < 0.001).
PGC provides a higher response rate, but the 3.1-month survival benefit did not reach statistical significance. These results suggest that new approaches will be needed in order to realize improvements in the survival of incurable urothelial cancer.
 Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, and de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/Gemcitabine and Gemcitabine/Cisplatin in Patients with Locally Advanced or Metastatic Urothelial Cancer without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol 2012;30(10):1107-1113.