Capecitabine +best supportive care (BSC) or erlotinib +BSC has overall survival (OS) benefit over BSC alone in unresectable/metastatic gall bladder cancer (GBC) patients with ECOG PS-III. Results from a phase II randomised controlled trial (RCT)

Background Gemcitabine with platinum is regarded as the standard of care in patients with unresectable and/or metastatic disease with good performance status (PS). There is no standard of care for poor PS patients. A report from M.D.A.C.C. stated a median OS of only one month in GBC patients with poor PS. Erlotinib and capecitabine, both have shown efficacy in metastatic GBC. There has been no RCT to date in GBC patients with poor PS. With limited data showing the activity of erlotinib and capecitabine, we conducted this RCT to evaluate the efficacy and toxicity of these drugs in this patient cohort. Methods This is an ongoing open-label, phase II/III RCT (phase II part of the study is complete).The primary objective is to determine if erlotinib (150 mg/d PO )+ BSC or capecitabine (625 mg/m2 BD PO) + BSC has an OS benefit compared to BSC alone in patients with unresectable/metastatic GBC with ECOG PS III. A total of 51 patients with histopathologically confirmed GBC, age >/=18 years, with adequate organ functions (S. bilirubin 50 ml/min/1.73m2) were randomised. Patients were followed up q2wk in first month and q4wk thereafter. Toxicity was assessed using CTCAE v4.1. Radiological response evaluation (as per RECIST v1.1) was done at 8-10 weeks/earlier if clinically indicated, QoL assessment (using EORTC QLQ-C30 BIL21 ) was done at baseline and at 6-8 weeks. Intervention was continued until progression/unacceptable toxicity. Serial evaluation for OS in all three arms was done. Initially the study was started as a phase II RCT, an interim pre-planned analysis was done after completion of phase II. Results The median OS in capecitabine +BSC arm (n = 19) was 209 days, relotinib +BSC arm(n = 14) was 105 days and BSC alone arm was 71 days (p value 0.022). Only 2 patients had grade III diarrhea with erlotinib. There were no drug-related SAEs. Conclusions There is a statistically significant OS benefit of capecitabine+BSC or erlotinib+BSC over BSC alone in unresectable/metastatic GBC patients with ECOG PS III. Results will be updated upon completion of phase III. Clinical trial identification CTRI/2019/04/018860. Legal entity responsible for the study The authors. Funding All India Institute of Academic Sciences. Disclosure All authors have declared no conflicts of interest.