Chemoradiation Prolongs OS, Maintains QOL in Advanced Gallbladder Cancers

After a median follow-up of 12 months, the median overall survival in the chemoradiation arm was 10 months vs 4 months in the observation arm.

Chemoradiotherapy (CTRT) prolonged survival and maintained quality of life (QOL) vs observation among patients in a low-middle-income setting with advanced gallbladder cancers (GBCs) who responded to first-line chemotherapy but were ineligible for resection, according to findings from the phase 3 RACE-GB trial (NCT05493956) published in the International Journal of Radiation Oncology, Biology, and Physics.¹

Efficacy results revealed that after a median follow-up of 12 months (IQR, 10-60), the median overall survival (OS) in the CTRT arm was 10 months (95% CI, 8.3-11.7) vs 4 months (95% CI, 3.0-4.9) in the observation arm (HR, 0.43; 95% CI, 0.32-0.62; P <.001). Additionally, the 1-year OS rates were 39.7% (95% CI, 28%-52%) vs 7.5% (95% CI, 2.4%-16.6%) in each respective arm (HR, 0.30; 95% CI, 0.0-0.82; P = .000). The respective 2-year OS rates were 5% (95% CI, 0.9%-12.4%) vs 3% (95% CI, 0.36%-10.4%; HR, 0.30; 95% CI, 0.362-0.820; P = .000).

Additionally, the median progression-free survival (PFS) in the CTRT vs observational arms was 7 months (95% CI, 5.2-8.7) vs 1 month (95% CI, 0.11-1.8). Progression as an event before death occurred in 86.8% vs 95.5% of respective patients, with the only important clinical factor being random assignment per univariate analysis (HR, 0.47; 95% CI, 0.33-0.67; P ≤.001).

“In this study, consolidation CTRT led to a clear separation of survival curves after randomization that lasted 24 months, and thereafter those patients who underwent extended cholecystectomy in both arms had long-term survivals,” lead author Sushma Agrawal, MD, DNB, professor of radiation oncology at the Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, India, wrote in the publication with study coinvestigators.¹ “A major factor in the assessment of the efficacy of CTRT is its ability to control local disease. CTRT resulted in a significantly lower incidence of local disease progression (39%) compared with the observation arm (75%), and this led to a significant prolongation of the PFS and OS compared with the observation arm.”

Patients with advanced GBC and a Karnofsky performance status score of at least 70, BMI greater than 15 kg/m², and normal organ and marrow function who responded to 4 cycles of chemotherapy were randomly assigned 1:1 to receive CTRT (n = 68) or undergo observation (n = 67). CTRT delivery occurred through 3-dimensional-conformal radiation, with a target dose of 45 Gy in 25 fractions to GBC and lymphatics followed by a 9 Gy boost to the GBC mass, and concurrent capecitabine at 1250 mg/m² for up to 6 cycles.² Patients in the observational arm were observed until evidence of disease progression.

Between the observation and CTRT arms, the median age was 54 years (IQR, 46-64) vs 52 years (IQR, 45-62), and 60% vs 63% of patients were female. The mean Charlson Comorbidity Index was 1.63 vs 1.5 in the respective arms, and 24% vs 31% underwent stenting. A total of 55% vs 56% of the respective arms had T4 disease, and 42% vs 38% had N2 disease.

QOL data showed that there was no significant change in the FACT-Hep Trial Outcome Index (TOI) score between type of treatment (P = .099) or interaction with time (P = .316). Additionally, TOI scores appeared consistent over time in the CTRT arm (P = .459) vs the observation arm, where TOI scores fell after 3 months from baseline (P = .002).

The most common treatment-related toxicities leading to death in the CTRT arm were radiation-induced liver disease (12%) and gastrointestinal bleeding (5.8%). Furthermore, second-line systemic therapy was given to 30.8% of the CTRT arm vs 16.4% of the observational arm.

References

1. Agrawal S, Kapoor V, Rahul R, Singh A, Mishra P, Saxena R. A randomized study of consolidation chemoradiotherapy versus observation after first-line chemotherapy in advanced gallbladder cancers: RACE-GB study. Int J Radiation Oncol Biol Phys. 2025;122(1):10-18. doi:10.1016/j.ijrobp.2024.11.099
2. A randomised study of consolidation CTRT versus observation after first line chemotherapy in advanced gallbladder cancer (RACE-GB). ClinicalTrials.gov. Updated September 9, 2022. Accessed April 18, 2025. https://tinyurl.com/3tv9udwc