Business
In the first randomized controlled trial of its kind, researchers found that adding chemoradiation to adjuvant chemotherapy did not improve outcomes in patients with resected gallbladder cancer.
Results from the phase 3 ACCELERATE trial were presented at the Gastrointestinal Cancers Symposium (GICS) 2025 by Atul Sharma from the All India Institute of Medical Sciences, New Delhi, India.
Although rare, gallbladder cancer has a poor prognosis, with only about 20% of patients surviving 5 years after curative resection, raising the need for more effective treatments.
“This is the first prospective trial to assess adjuvant chemoradiation in resected gallbladder cancer,” said Sharma during his presentation. “We designed this study to answer whether adding chemoradiotherapy to chemotherapy improves recurrence-free survival in this population.”
Business Study Design
The open-label, multicenter, phase 3 trial randomized 94 patients with resected gallbladder cancer to receive either chemotherapy alone (arm 1) or chemotherapy plus chemoradiation (arm 2). Chemotherapy consisted of either modified gemcitabine-oxaliplatin or gemcitabine-cisplatin. In the experimental arm, patients received three cycles of chemotherapy followed by chemoradiation (45 Gy with concurrent capecitabine) and then additional cycles of chemotherapy. Although the trial aimed to enroll 200 patients (100 per arm), slow accrual and the COVID-19 pandemic led to early closure.
In her discussion of the ACCELERATE trial, Namrata Vijayvergia, MD, of the Fox Chase Cancer Center, Philadelphia, who was not involved in the study, praised the researchers for conducting a randomized trial in this rare cancer type.
“Doing a randomized trial in gallbladder cancer in a resource-limited setting without support is highly commendable,” she noted. Although gallbladder cancer is rare, its incidence is relatively high in certain regions, including northern India, she added.
Business Key Findings
The study showed that the addition of chemoradiation to adjuvant chemotherapy did not significantly improve recurrence-free survival (RFS), which was the primary endpoint of the study. The median RFS was not estimable in the chemotherapy-alone arm and was 34.39 months in the chemoradiation arm (P = .202). Similarly, median overall survival was not estimable in the chemotherapy arm and was 34.56 months in the chemoradiation arm (P = .123).
The median RFS of 34.39 months in the combination arm exceeded typical expectations, according to Vijayvergia.
“This is more than what we typically see in the adjuvant setting, where RFS is around 24-16 months,” she explained in the interview. “All patients had R0 resection, which may delay the recurrence overall, but the overall survival is similar to that in published data.”
Business Limitations
Vijayvergia highlighted some imbalances between the treatment arms that might have influenced the results, including the proportions of patients with a higher stage and node positivity having been higher in the chemoradiotherapy arm.
She also pointed out that the number of chemotherapy cycles “was much higher in the chemotherapy-alone arm compared to the chemoradiotherapy arm.”
Sharma acknowledged that the imbalances between treatment arms in terms of disease stage and chemotherapy completion rates, as well as the premature closure of enrollment and potential influence of COVID-19 on the results, are limitations that complicate the interpretation of the findings.
Sharma also noted that all centers involved in the study were in India, where gallbladder cancer is relatively common, which may limit the generalizability of the findings. Despite this, Vijayvergia noted that the study findings may have broader implications for global practice.
“Trials like ACCELERATE give us an opportunity to study this rare cancer as a separate entity rather than clubbing it with other biliary cancer,” Vijayvergia noted in the interview. “The risk factors may be slightly different, but the results from ACCELERATE align with what we see with western trials; hence, I think we can extrapolate results easily.”
Business Implications and Future Directions
According to Vijayvergia, the results of the ACCELERATE trial align with previous evidence suggesting that systemic chemotherapy remains the cornerstone of adjuvant treatment for gallbladder cancer. She said the findings support the current standard of care using systemic therapy alone for most patients while leaving room for consideration of chemoradiation in selected cases, particularly those with positive margins.
“Systemic spread is the biggest risk in gallbladder cancer, and radiation may play a role in selected patients, like those with R1 resection,” she noted.
Despite the limitations of the study, Vijayvergia expressed confidence in the findings.
“The trial’s early closure definitely affected the power of the study, but the difference is so clearly seen that a bigger study would have given the same results — and it may not be feasible to do this again,” she stated in the interview.
Vijayvergia also emphasized that the ACCELERATE trial provides important benchmark data for future studies.
“We have randomized data of 95 patients, which is gallbladder specific in a resource-limited setting, which provides us with a benchmark for our practice in future trials,” she said.
Looking ahead, both speakers emphasized the need for novel therapeutic approaches.
Sharma noted during his presentation that “there’s an urgent need to develop studies with novel targets in this disease to improve outcomes.”
Vijayvergia expanded on this point, explaining that the focus appears to be shifting toward incorporating targeted therapies and immunotherapy approaches that have shown promise in the metastatic setting into earlier-stage treatment strategies.
“We have revolutionized the care of metastatic biliary cancer with so many targeted agents that have come in, and I think it is time to bring them into the adjuvant setting. I especially point out the HER2-positive [human epidermal growth factor receptor 2–positive] HER2 drugs and the PD1 drugs because they’re approved in the metastatic setting,” she said.
This study was independently supported. Sharma reported receiving honoraria from AstraZeneca, Dr Reddy’s Labs, Merck Serono, MSD Oncology, Pfizer India Limited, Roche India, and Zydus Lifesciences; speakers’ bureau from Merck Serono and Zydus Lifesciences; and stock and other ownership interests from Divis Lab, Dr Reddy’s Labs, Glenmark (I), Jyothy Labs, Laurus Labs, Shilpa Medicare, Zydus Wellness, and Zydus Lifesciences. Vijayvergia reported receiving consulting or advisory fees from Exelixis, RayzeBio, and Taiho Oncology; honoraria from Guidepoint Global; and research funding from Bristol-Myers Squibb/Medarex, ITM Isotope Technologies Munich, Oryzon Genomics, Puma Biotechnology, and Zymeworks.
Christos Evangelou, PhD, is a freelance medical writer and science communications consultant.
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