Adjuvant Gemcitabine Plus Oxaliplatin vs Surveillance in Resected Biliary Tract Cancer
In a French phase III trial (PRODIGE 12-ACCORD 18-UNICANCER GI) reported in the Journal of Clinical Oncology, Edeline et al found that adjuvant gemcitabine plus oxaliplatin (GEMOX) did not significantly improve relapse-free survival vs surveillance following resection for localized biliary tract cancer. As noted by the investigators, no standard adjuvant treatment currently is recommended in this setting.
Study Details
In the open-label trial, 194 eligible patients from 33 sites in France were randomly assigned between July 2009 and February 2014 to receive within 3 months after R0 or R1 resection GEMOX (gemcitabine at 1,000 mg/m2 on day 1 and oxaliplatin at 85 mg/m2 infused on day 2 of a 2-week cycle) for 12 cycles (n = 95) or surveillance (n = 99). The primary endpoints were relapse-free survival and time to deterioration in health-related quality of life (HRQOL), with the hypothesis that GEMOX would improve relapse-free survival while maintaining HRQOL.
HRQOL was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Cancer Quality of Life Questionnaire-C30, version 3.0. The trial was designed to detect a difference in median relapse-free survival from 18 months in the surveillance group to 30 months in the GEMOX group. The planned hazard ratio [HR] for the GEMOX vs surveillance group was 0.6.
Relapse-Free Survival and HRQOL
Median follow-up was 46.5 months. Median relapse-free survival was 30.4 months in the GEMOX group vs 18.5 months in the surveillance group (hazard ratio [HR] = 0.88, P = .48). Relapse-free survival rates were 66% vs 64% at 12 months, 53% vs 46% at 24 months, 47% vs 43% at 36 months, and 36% vs 33% at 48 months. Median overall survival was 75.8 months vs 50.8 months (HR = 1.08, P = .74). Overall survival rates were 86% vs 94% at 12 months, 69% vs 76% at 24 months, 60% vs 65% at 36 months, and 51% vs 52% at 48 months.
Grade 3 adverse events were observed in 62% of the GEMOX group vs 18% in the surveillance group, and grade 4 adverse events were observed in 11% vs 3% (P < .001).
The investigators concluded, “There was no benefit of adjuvant GEMOX in resected [biliary tract cancer] despite adequate tolerance and delivery of the regimen.” They noted, “The planned HR of 0.6 [for GEMOX vs surveillance] was ambitious, which may suggest that the trial was underpowered. However, the observed HR of 0.88 suggests a low chance of clinically significant benefit, and the median [relapse-free survival] was achieved at a plateau with the largest separation between the curves, meaning that the median was less representative of the true difference than the HR.”
Julien Edeline, MD, PhD, of the Centre Eugène Marquis, Rennes, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Programme Hospitalier de Recherche Clinique (PHRC 2009) and Ligue Nationale Contre le Cancer. The study authors' full disclosures can be found at jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
