ACCELERATE Trial: Evaluating Adjuvant Therapy in Resected Gallbladder Cancer

The ACCELERATE trial, a multicenter, phase III randomized controlled study, explored the role of adjuvant chemotherapy (ChT) versus chemotherapy combined with chemoradiation (CRT) in improving outcomes for patients with resected gallbladder cancer. Despite promising design, the trial faced challenges, including premature closure due to slow accrual and the COVID-19 pandemic, yielding inconclusive results regarding the potential benefit of adding CRT to ChT. Atul Sharma, MBBS, MD, presented the trial results at the American Society of Clinical Oncology 2025 Gastrointestinal Cancers Symposium.

Study Design and Patient Population
The trial enrolled 94 patients with R0 or R1 resected gallbladder cancer, who were randomized into two arms: ChT alone (Arm 1) or ChT followed by CRT (Arm 2). Chemotherapy regimens included either mGemOx (gemcitabine plus oxaliplatin) or GemCis (gemcitabine plus cisplatin). Patients in Arm 2 received three cycles of ChT followed by 45 Gy of radiation with concurrent capecitabine and an additional two to three cycles of ChT. The primary endpoint was relapse-free survival (RFS).

Key Findings
RFS was not estimable in Arm 1 but was 34.39 months in Arm 2 (P=.202). Similarly, overall survival (OS) was not estimable in Arm 1 and was 34.56 months in Arm 2 (P=.123). The mean RFS was 51.96 months for Arm 1 and 43.99 months for Arm 2, with no statistically significant differences observed.

Completion rates for five to six cycles of ChT were higher in Arm 1 (85.7%) than in Arm 2 (62.2%). Arm 1 also showed higher incidences of diarrhea (P=.021) and peripheral neuropathy (P=.001). Mortality due to disease progression was higher in Arm 2 (44.44%) than in Arm 1 (28.57%).

One patient in each arm died due to treatment-related toxicity, emphasizing the need for close monitoring of adverse events, particularly with combination regimens.

Implications for Clinical Practice
The findings from the ACCELERATE trial indicate that adding CRT to ChT does not significantly improve RFS or OS for patients with resected gallbladder cancer. Although CRT may offer potential benefits for patients with other gastrointestinal malignancies, its lack of efficacy in this study suggests that chemotherapy alone remains the standard adjuvant approach for gallbladder cancer following surgery.

The study highlights the need for larger, adequately powered trials to determine whether CRT has a role in improving outcomes for patients with resected gallbladder cancer.