Abstract 55P
Background
While gemcitabine-based chemotherapy (GBCT) is the first-line standard of care for patients with advanced biliary tract cancers (BTC), adjuvant phase III studies (BCAT and PRODIGE 12) failed to show benefit, possibly because of a lower power due to fewer patients (n=225 and n=194) compared to the adjuvant capecitabine BILCAP trial (n=447). We performed a pooled analysis of both GBCT adjuvant studies.
Methods
Individual patient data pooled analysis of all patients included in BCAT and PRODIGE 12. BCAT randomized patients with extrahepatic cholangiocarcinoma (CC) to single-agent gemcitabine for 6 months or observation. PRODIGE 12 randomized patients with all BTC subtypes to gemcitabine-oxaliplatin combination for 6 months or observation. Combined analysis was done using Kaplan-Meier curves and a Cox regression model stratified on the trial. We studied overall survival (OS) and relapse-free survival (RFS).
Results
212 vs 207 patients were randomized in the GBCT vs observation arms. Mean age (66.3 vs 64.7), sex (male, 63.2% vs 63.8%), R1 status (11.3% vs 12.6%), N1 status (36.3% vs 34.8%), primary tumor location (distal CC, 43.9% vs 41.1%; perihilar CC, 28.8% vs 27.1%; intrahepatic CC, 19.3% vs 21.7%; gallbladder carcinoma, 8.0% vs 10.1%) were balanced between arms. There were differences between populations included in the trials (p<0.001 for age, sex, N1 status, primary tumor location and total gemcitabine dose). The median follow-up was 5.5 years. After 258 RFS events, there was no difference in RFS: median 2.9 years (95%CI: 1.8-3.8) for GBCT vs 2.1 years (95%CI: 1.4-3.4) for observation (log-rank p=0.45; hazard ratio (HR)=0.91 [95%CI 0.71-1.16]; p=0.46). Respective RFS rates at 5 years were 40.8% (95%CI: 33.9%-47.5%) vs 36.6% (95%CI: 29.8%-43.4%). After 201 deaths, there was no difference in OS: median 5.1 years (95%CI: 3.4-7.0) for GBCT vs 5.0 years (95%CI: 3.9-NA) for observation (log-rank p=0.83; HR=1.03 [95%CI: 0.78-1.35]; p=0.85). Respective OS rates at 5 years were 50.5% (95%CI: 43.1%-57.4%) vs 49.3% (95%CI: 41.6%-56.5%).
Conclusions
With 419 patients included, this pooled analysis of BCAT and PRODIGE 12 did not show any improvement in RFS or OS. GBCT should not be used as an adjuvant treatment for BTC.
Clinical trial identification
PRODIGE 12: EudraCT 2008-004560-39. BCAT: UMIN 000000820.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer.
Funding
Programme Hospitalier de Recherche Clinique (PHRC-2009) and Ligue Nationale Contre le Cancer.
Disclosure
J. Edeline: Honoraria (self), Research grant/Funding (self): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Beigene; Honoraria (self): Bayer; Honoraria (self): Eisai; Honoraria (self): Ipsen; Honoraria (self): BTG; Honoraria (self): Roche. M. Benabdelghani: Honoraria (self): Servier; Honoraria (self): Ipsen; Honoraria (self): Amgen; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Bayer. P. Hammel: Honoraria (self): BMS; Honoraria (self): Servier; Honoraria (self): AstraZeneca. D. Malka: Honoraria (self): Amgen; Honoraria (self): Bayer; Honoraria (self): MSD; Honoraria (self): Merck Serono; Honoraria (self): Servier; Honoraria (self): Agios; Honoraria (self): Incyte; Honoraria (self): Novartis; Honoraria (self): Sanofi; Honoraria (self): Roche; Honoraria (self): HalioDX; Honoraria (self): Pierre Fabre Oncologie. All other authors have declared no conflicts of interest.