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).

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/m2 per day, on days 1 to 14 plus intravenous irinotecan, 200 mg/m2, on day 1 or intravenous irinotecan, 240 mg/m2, 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.

TRIAL REGISTRATION: CTRI/2017/10/010112.