Efficacy of Capecitabine Plus Irinotecan vs Irinotecan Monotherapy as Second-line Treatment in Patients With Advanced Gallbladder Cancer A Multicenter Phase 2 Randomized Clinical Trial (GB-SELECT)

Question Does combination chemotherapy with capecitabine plus irinotecan (CAPIRI) improve overall survival (OS) compared with irinotecan monotherapy in patients with advanced gallbladder cancer who have received prior treatment with a gemcitabine-platinum regimen? Findings Use of a CAPIRI regimen did not improve OS compared with irinotecan; more patients in the CAPIRI arm required dose modification compared with those in the irinotecan arm. Meaning Combination chemotherapy did not improve OS compared with single-agent chemotherapy in previously treated patients with advanced gallbladder cancer. This randomized clinical trial compares the efficacy of capecitabine plus irinotecan vs irinotecan alone in patients with advanced gallbladder cancer who had disease progression after gemcitabine-based first-line treatment. Importance There is therapeutic uncertainty regarding use of combination or single-agent chemotherapy in the treatment of patients with gallbladder cancer who experience disease progression after first-line chemotherapy. Objective To compare the efficacy of capecitabine plus irinotecan (CAPIRI) vs irinotecan (IRI) alone in patients with advanced gallbladder cancer (GBC) who have disease progression after gemcitabine-based first-line treatment. Design, Setting, and Participants The GB-SELECT trial was a multicenter, open-label, phase 2, randomized clinical trial of CAPIRI vs IRI alone for treatment of gallbladder cancer in patients who had disease progression after prior gemcitabine-based chemotherapy.The study was carried out in 2 tertiary care institutions in India. Patients aged between 18 and 70 years with histopathologic diagnosis of adenocarcinoma gallbladder, advanced or metastatic disease, previous treatment with gemcitabine-based chemotherapy, adequate hematologic, liver, and renal functions, and ECOG performance status of 1 or less were included in the study between August 2018 and January 2020. The data were analyzed for this report with cutoff on May 19, 2020. Interventions Patients were randomized 1:1 to receive capecitabine, 1700 mg/m(2) per day, on days 1 to 14 plus intravenous irinotecan, 200 mg/m(2), on day 1 or intravenous irinotecan, 240 mg/m(2), on day 1, in 21-day cycles until disease progression or unacceptable toxic effects. Main Outcomes and Measures The primary end point was overall survival (OS) at 6 months. The secondary end points were progression-free survival and quality of life. Results A total of 98 patients were randomized, 49 in each arm, with median (range) age of 51 (29-70) years, with 60 (61%) being women. In the CAPIRI vs IRI arms, the number of deaths at 6 months, 6-month OS, and median OS were 35, 34, 38.4% (95% CI, 24.2%-52.6%) and 5.16 (95% CI, 4.26-6.06) months vs 34, 29, 54.2% (95% CI, 39.4%-69.0%) and 6.28 (95% CI, 4.25-8.30) months, respectively, with a hazard ratio of 1.02 (95% CI, 0.64-1.49, P = .93). There were no chemotherapy-related deaths but more patients required dose modification in CAPIRI compared with the IRI arm (13 [27%] vs 4 [9%], respectively, P = .03). Conclusions and Relevance There was no significant difference in OS between treatment with capecitabine plus irinotecan or irinotecan alone among previously treated patients with gallbladder cancer. Single-agent irinotecan should be the preferred treatment option for such patients.