The addition of chemoradiation (CRT) to chemotherapy did not improve relapse-free survival (RFS) in patients with resected gallbladder cancer, according to results from the phase 3 ACCELERATE trial presented at the 2025 ASCO Gastrointestinal Symposium. The study, which randomized 94 patients, aimed to determine if CRT following chemotherapy could improve outcomes in this patient population, but the results indicated no significant benefit.
The ACCELERATE trial randomly assigned patients to either chemotherapy alone (gemcitabine and oxaliplatin or gemcitabine and cisplatin) or chemotherapy plus CRT (capecitabine during radiation, followed by chemotherapy). The primary endpoint was RFS, with overall survival (OS) and toxicity as secondary endpoints. Patients eligible for enrollment had undergone radical cholecystectomy and had pT2 or higher or N+ disease.
Key Findings from the ACCELERATE Trial
Kaplan Meier estimates for RFS showed a hazard ratio (HR) of 1.59 (95% CI, 0.83-3.03) and an adjusted HR of 1.09 (95% CI, 0.54-2.17) when comparing the combination arm to the chemotherapy-alone arm. In the chemotherapy-alone arm, 16 patients experienced disease progression versus 22 in the combination arm. The median survival was 52.7 months.
Regarding overall survival (OS), the HR was 1.60 (95% CI, 0.86-2.95), and the adjusted HR was 1.16 (95% CI, 0.61-2.22). These results suggest that the addition of CRT did not provide a survival advantage in this study.
Adverse Events and Tolerability
The trial also assessed the toxicity of the treatment regimens. All-grade diarrhea occurred in 27 patients in the chemotherapy arm and 14 patients in the CRT plus chemotherapy arm, with grade 3/4 events occurring in 2 versus 1 patient, respectively. Hepatic adverse events were observed in 25 versus 18 patients (all grades) and 1 versus 3 patients (grade 3/4). Peripheral neuropathy was more common in the chemotherapy arm, with 31 patients experiencing all-grade events compared to 12 in the combination arm.
Expert Commentary
"This is the first prospective trial to address the issue of adjuvant CRT in gallbladder cancer," said Dr. Atul Sharma from All India Institute of Medical Sciences, New Delhi, India, during the presentation of the data. However, Dr. Sharma also noted, "Since accrual could not be completed, a larger trial is needed to address this important issue."
Dr. Sharma further commented on the unexpected outcomes, stating, "It is unclear whether the lack of improvement in the experimental arm was influenced by unexpectedly favorable outcomes in the standard arm. Additionally, it remains uncertain if the results would have differed if the study completed planned enrollment."
