130351-144

Final results of EORTC intergroup randomized phase III trial comparing immediate versus deferred chemotherapy after radical cystectomy in patients with pT3T4 and/or N+ M0 transitional cell carcinoma (TCC) of the bladder.

Subcategory: 
Category: 
Genitourinary (Nonprostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Nonprostate) Cancer
Abstract Number: 

4500

Citation: 

J Clin Oncol 32:5s, 2014 (suppl; abstr 4500)

Author(s): 

Cora N. Sternberg, Iwona Anna Skoneczna, Jan M. Kerst, Sophie D. Fossa, Peter Albers, Mads Agerbaek, Herlinde Dumez, Maria De Santis, Christine Theodore, Michael Gordon Leahy, John D. Chester, Antony Verbaeys, Armelle Caty, Gedske Daugaard, Sandrine Marreaud, Samantha Cambier, Richard Sylvester; Hospital San Camillo-Forlanini, Rome, Italy; Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland; The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway; Düsseldorf University, Duesseldorf, Germany; Aarhus University Hospital, Aarhus, Denmark; U.Z. Leuven, Gasthuisberg Campus, Leuven, Belgium; LBI-ACR-VIEnna and KFJ Spital, Wien, Austria; Institut Gustave Roussy, Villejuif, France; St James's University Hospital, Leeds, United Kingdom; University Hospital Gent, Gent, Belgium; Centre Oscar Lambret, Lille, France; Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; European Organisation for Research and Treatment of Cancer, Brussels, Belgium; European Organization for Research and Treatment of Cancer, Brussels, Belgium; European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: Patients (pts) with muscle invasive TCC of the bladder have poor overall survival (OS) due to systemic disease at diagnosis. This randomized intergroup phase III trial compared immediate vs deferred chemotherapy after radical cystectomy in pts with pT3T4 and/or N+ M0 TCC of the bladder. Methods: Within 90 days after cystectomy, pts were randomized to 4 cycles of GC, HD-MVAC or MVAC adjuvant chemotherapy or 6 cycles of deferred chemotherapy at relapse. Main endpoint was OS with PFS a secondary endpoint. Analysis was by intent-to-treat using Cox models stratified by group and adjusted for T stage (pT1T2 vs pT3T4) and nodal status (N- vs N+). Results: 284 of 660 pts were enrolled in 63 sites from 13 countries from 4/2002 to 8/2008 when the trial closed for poor accrual. Follow up (f/u) continued for 5 yrs to 8/2013. Pt characteristics were well balanced in the treatment groups; median age was 61 yrs with similar pT and nodal status (70% N+). Most received GC. Median and maximum f/u is 7.0 and 10.4 yrs in the immediate and 7.2 and 10.6 yrs in the deferred arm. An IDMC reviewed the trial twice and recommended continuation. 176 pts (62.0%) progressed or died, 73 (51.8%) on the immediate and 103 (72.0%) on the deferred arm. Median and 5 yr PFS are 2.9 yrs and 46.8% on the immediate and 0.9 yrs and 29.5% on the deferred arm (p< 0.0001). 148 pts (52.1%) died, 66 (46.8%) on the immediate and 82 (57.3%) on the deferred arm. Median and 5 yr OS are 6.8 yrs and 53.6% on the immediate and 4.6 yrs and 47.7% on the deferred arm, HR=0.78 (95.09% CI: 0.56, 1.10, p=0.13). Grade 3/4 AEs in the immediate arm included myelosuppression (26%), neutropenia (38%) and thrombocytopenia (28%). One pt died due to toxicity in the immediate arm. Conclusions: This is the largest reported randomized trial of adjuvant chemotherapy in pts with muscle invasive bladder cancer. Immediate adjuvant cisplatin based combination chemotherapy led to a statistically significant improvement in the secondary endpoint PFS and a non-significant decrease of 22% in the risk of death after radical cystectomy, the primary endpoint. The 2005 IPD meta-analysis should be updated. Clinical trial information: NCT00028756.