Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986

Abstract

Purpose This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible (“unfit”) for cisplatin chemotherapy. Patients and Methods The primary objective of the phase III part of this study was to compare the overall survival (OS) of chemotherapy-naive patients with measurable disease and an impaired renal function (glomerular filtration rate < 60 but > 30 mL/min) and/or performance score of 2 who were randomly assigned to receive either gemcitabine/carboplatin (GC) or methotrexate/carboplatin/vinblastine (M-CAVI). To detect an increase of 50% in median survival with GC compared with M-CAVI (13.5 v 9 months) based on a two-sided log-rank test at error rates α = .05 and β = .20, 225 patients were required. Secondary end points were overall response rate (ORR), progression-free survival (PFS), toxicity, and quality of life. Results In all, 238 patients were randomly assigned by 29 institutions over a period of 7 years. The median follow-up was 4.5 years. Best ORRs were 41.2% (36.1% confirmed response) for patients receiving GC versus 30.3% (21.0% confirmed response) for patients receiving M-CAVI (P = .08). Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm (P = .64). There was no difference in PFS (P = .78) between the two arms. Severe acute toxicity (death, grade 4 thrombocytopenia with bleeding, grade 3 or 4 renal toxicity, neutropenic fever, or mucositis) was observed in 9.3% of patients receiving GC and 21.2% of patients receiving M-CAVI. Conclusion There were no significant differences in efficacy between the two treatment groups. The incidence of severe acute toxicities was higher for those receiving M-CAVI.

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

“…68,80 However, in patients with disease that relapses after this type of chemotherapy, the median survival is reduced to 5 to 7 months. 81 Several new agents, notably checkpoint inhibitors for the treatment of metastatic urothelial carcinoma, have data supporting improved outcomes compared with standard therapies.…”

Early Oncologic Failure after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

“…Despite aggressive management, more than half of patients with MIBC will relapse (locally or systemically), usually within the first 2 years after surgery with deleterious impact on survival 5,6 . These relapses may be related to the disease aggressiveness or breaching of oncologic principles during surgery.…”

Systemic Therapy for Bladder Cancer Finally Comes into a New Age

“…The ORR was 36%, with a median overall survival (mOS) of 7.2 months, both reasonable for this population. A Phase II/III EORTC 30986 trial randomized cisplatin-ineligible patients to two different carboplatin-based regimens: GCa and methotrexate/carboplatin/vinblastine (MCAVI) [55]. The ORR showed a nonsignificant trend to improvement in the GCa group (41.2 vs 30.3%; p = 0.08), but there was no difference in mOS (9.3 vs 8.1 months; p = 0.64).…”