Adjuvant chemotherapy for biliary tract cancer using GEMOX (gemcitabine/oxaliplatin) was feasible, but did not result in an improved recurrence-free survival or quality of life compared with surveillance in the phase III PRODIGE 12-ACCORD 18 trial (abstract 225).
“In the PRODIGE 12 trial we showed that adjuvant GEMOX was feasible and toxicities were as expected without any detrimental effect on global quality of life,” said Julien Edeline, MD, of Oncology Medical Eugene Marquis Comprehensive Cancer Center, Rennes, France. “However, adjuvant GEMOX was not associated with an improvement in recurrence-free survival.”
Edeline presented the results of the phase III trial at the 2017 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, held January 19–21 in San Francisco.
According to Edeline, there is a high risk of relapse after surgery for localized biliary tract cancer and there is currently no standard adjuvant treatment. Prior research has shown that gemcitabine combined with cisplatin improved overall survival in these patients. The combination of gemcitabine and oxaliplatin is considered to be an active regimen based on data from phase II trials.
This phase III trial was designed to test if GEMOX would delay disease recurrence without any effect on patient quality of life. The study included 196 patients from 33 French centers. Patients were randomly assigned within 3 months of disease resection to GEMOX 85 for 12 cycles (arm A) or surveillance every 3 months for 2 years and then every 6 months for 3 years (arm B). There were co-primary endpoints of recurrence-free survival and health-related quality of life.
With a median follow-up of 44.3 months, 54 recurrence-free survival events occurred in GEMOX arm compared with 64 in the surveillance arm. With a hazard ratio of 0.83 (95% CI, 0.58-1.19; P = 0.31), there was no significant difference in recurrence-free survival between the two arms. The median recurrence-free survival was 30.4 months for patients assigned GEMOX compared with 22.0 months for patients assigned surveillance. Four-year recurrence-free survival was 39.3% for GEMOX compared with 33.2% for patients assigned surveillance.
The researchers also studied relapse-free survival according to predefined subgroups and found no subgroup for either primary disease site or extent of resection that might benefit from adjuvant GEMOX therapy.
Analysis of the health-related quality of life showed no difference in outcomes at 12 months or at 24 months between the two study arms.
As expected, assignment to chemotherapy increased the occurrence of grade 3 or higher adverse events—both hematological and nonhematological—compared with surveillance. One patient died in each arm during treatment. The most common grade 3 or higher toxicities in the chemotherapy arm were peripheral neuropathy and neutropenia.