A Randomized Study of Consolidation Chemoradiotherapy Versus Observation After First-line Chemotherapy in Advanced Gallbladder Cancers: RACE-GB study.

Purpose: Chemotherapy (CT) is the standard of care for patients presenting with unresectable advanced gallbladder carcinoma (GBC) but their prognosis remains poor. The value of consolidation CT and radiation therapy (RT) after initial CT is uncertain. We, therefore, conducted a single-center open-label randomized trial evaluating consolidation CTRT versus observation after 4 cycles of CT in patients whose disease did not progress during CT (partial responders/stable disease).

Methods And Materials: Responders to 4 cycles of CT were randomized (1:1) to CTRT versus observation (n = 135). CTRT was delivered using 3-dimensional-conformal RT (Field in the field when required) along with concurrent capecitabine. The dose of RT was 45 Gy in 25 fractions to GBC and lymphatics followed by a boost of 9 Gy in 5 fractions to the GBC. The primary endpoint was overall survival (OS) which was calculated from the date of randomization.

Results: A total of 67 patients were randomized to observation and 68 to CTRT. Consolidation CTRT led to an improvement in median OS from 4 to 10 months (hazard ratio, 0.43; 95% CI, 0.32-0.62; P < .001). The actual median OS from accrual was 7 months (95% CI, 6.114-7.88 months) versus 13 months (95% CI, 11.13 -14.84 months). Adverse events (grade 3 or higher) because of CTRT were nausea (3%), anemia (9%), gastrointestinal bleeding (5.8%), and hepatotoxicity (13%). Functional Assessment of Cancer Therapy-General score and the Functional Assessment of Cancer Therapy-Hepatobiliary score did not deteriorate because of CTRT compared with observation (P values, .053 and .097).

Conclusions: To our knowledge, this is the first-ever randomized study in a low-middle-income country setting to demonstrate that consolidation CTRT significantly prolonged OS without deterioration in quality of life and should be the alternative standard of care in advanced unresectable GBC.