Nivolumab monotherapy and associations in the treatment of advanced unresectable biliary tract cancer (BTC): A systematic review and meta-analysis.

Abstract

e16216 Background: Patients with advanced unresectable BTC have a poor prognosis, and treatment options are limited and with variable response rates. Nivolumab (NIVO), a PD-1 inhibitor, has shown its effectiveness against multiple cancer types and has been tested as a therapeutic option in diverse settings and associations. Methods: We performed a systematic review and single arm meta-analysis of clinical trials of NIVO monotherapy or combined therapy in advanced unresectable BTC. PubMed, Embase, and Cochrane database were searched for clinical trials published up to May 1, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. The primary endpoints of interest were objective response rate (ORR = CR+PR) and disease control (DC = SD or better response) per RECIST v1.1, at any period of the trial. Results: Out of 80 database results, 6 clinical trials and 358 patients were included, all were using some form of NIVO therapy. Overall, NIVO and associations present an ORR = 13% (95% CI 0.08-0.16, I² = 23%, p = 0.26) and DC = 39% (95% CI 0.27-0.51, I² = 69%, p < 0.05). NIVO monotherapy present an ORR = 6% (95% CI 0.02-0.10, I² = 36%, p = 0.19) and DC = 28% (95% CI 0.04-0.51, I² = 87%, p < 0.001) while NIVO + ipilimumab association show an ORR = 11% (95% CI 0.004-0.22, I² = 76%, p < 0.05) and DC = 37% (95% CI 0.24-0.49, I² = 28%, p = 0.23). NIVO + gencitabine + cisplatin association trials reported an ORR within 13-18% and DC around 32%. This data suggests that associations of NIVO present higher efficacy in the treatment of BTC and should be considered among the first choices of therapy, however drug adverse effects tolerability might play an important part in the individualized patient care. Conclusions: There are marked limitations to the applicability of these findings in clinical practice, therefore a cautionary approach to this data is recommended, given their overall low statistical power, heterogenous study design, and tolerability to adverse effects. New trials of NIVO + associations with better standardized outcomes and comparative arms for different associations and populations will help to better clarify the effects of NIVO in the treatment of advanced unresectable BTC. [Table: see text]