Among patients with resected gallbladder cancer, the addition of chemoradiation (CRT) to chemotherapy treatment did not improve relapse-free survival (RFS), according to phase 3 ACCELERATE trial results, which were shared at the 2025 ASCO Gastrointestinal Symposium.
The median survival was 52.7 months. Estimates for RFS (93 patients) showed a hazard ratio (HR) of 1.59 and an adjusted HR (aHR) of 1. In the chemotherapy-alone arm, 16 patients had progression versus 22 in the combination arm. The estimate for RFS by CA 19.9 status (79 patients) included an HR of 6.49 and an aHR of 5.4.
Of note, 30 patients in the chemotherapy arm were alive compared with 21 in the CRT plus chemotherapy arm, with 18 and 24, respectively, having died in each arm. Causes of death included relation to disease (13 versus 20 patients), toxicity (1 versus 1 patient), or unknown causes (1 versus 1 patient).
“This is the first prospective trial to address the issue of adjuvant CRT in gallbladder cancer,” Dr. Atul Sharma, from All India Institute of Medical Sciences, New Delhi, India, stated during a presentation of the data. “Since accrual could not be completed a larger trial is needed to address this important issue.”
A total of 94 patients were randomly assigned to either the chemotherapy alone arm (49 patients) or the chemotherapy plus CRT arm (45 patients). In the chemotherapy alone arm, patients were given either 6 cycles of gemcitabine at a 900 milligrams per square meter (mg/m2) dose and oxaliplatin at a 80 mg/m2 dose, intravenously, on days 1 and 8 every three weeks; or gemcitabine at a 1000 mg/m2 dose and cisplatin at a 25 mg/m2 dose on days 1 and 8 every 3 weeks. The combination arm was given 3 cycles of chemotherapy plus CRT at 45 Gy in 25 fractions over 5 weeks with concurrent capecitabine at 825 mg/m2 twice a day during radiation days, and then another 2 to 3 cycles of chemotherapy. Patients who had a positive margin were given an additional 9 Gy boost.
All grade side effects for diarrhea occurred in 27 patients in the chemotherapy arm and 14 patients in the CRT plus chemotherapy arm, with grade 3 (severe) and 4 (life threatening or disabling) side effects occurring in 2 versus 1 patient. For hepatic, 25 versus 18 patients experienced all grade events and 1 versus 3 patients had grade 3 and 4 side effects. Regarding peripheral neuropathy, 31 versus 12 patients experienced all-grade side effects and none had grade 3 or 4 events.
The primary end point was RFS, and the secondary end points were OS and toxicity of chemotherapy and CRT.
Patients were eligible for enrollment if they had radical cholecystectomy, pT2 or higher or N+ disease or at least six lymph nodes that should have been dissected and microscopically examined. Participants were excluded if they were women of reproductive age not practicing contraception, those who were on other investigational drugs or had a history of carcinoma within the previous five years.
In the chemotherapy alone arm, the sample size calculation found a median RFS of 18 months. The hypothesis was that CRT would increase the median RFS from 18 to 28 months.
At the time of enrollment, 16 males and 32 females were in the chemotherapy alone arm versus 13 and 32 in the CRT plus chemotherapy arm. Pain was noted in 40 and 41 patients, respectively, an ECOG performance status of 1 was observed in in 37 and 36 patients, and a median age of 55 was observed in both arms.
Baseline parameters at enrollment also included diabetes in 8 patients versus 8 patients, hypertension in 9 versus 7, and more than 1 comorbidity in 6 versus 2 between the monotherapy and combination arms, respectively.
In the chemotherapy-alone arm, the most common disease stage was 2A (20 patients) vs 3A in the combination arm (19 patients). Additionally, 12 patients versus 16 patients were node positive.
In the chemotherapy arm, the most common number of chemotherapy cycles was 6 (35 patients). The majority did not have dose reductions (30 patients), and there were dose delays of up to 1 week (22 patients). In the combination arm, the most common number of chemotherapy cycles was 6 (19 patients). The majority of dose reductions were up to 25% (24 patients), and dose delays occurred up to 1 week (25 patients).
“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,” Sharma concluded.
Reference:
“Adjuvant chemotherapy or chemo-radiation in gallbladder cancer: A phase III randomized controlled study (ACCELERATE trial)”. Sharma A, et al. J Clin Oncol.
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