Researchers’ prior research indicated that the combination of modified gemcitabine and S-1 (GS) was an effective regimen for patients with advanced biliary tract cancer (ABTC). They present data from a single-arm phase II study of nivolumab plus modified GS (NGS) as frontline therapy for ABTC. Patients were given 80/100/120 mg of S-1 daily (depending on body surface area) on days 1-10 of a 2-week cycle, in addition to 240 mg of nivolumab and 800 mg/m2 of gemcitabine on day 1. The study’s primary outcome measure was the objective response rate (ORR). Targeted next-generation sequencing panels were used to investigate whether or not there is a connection between therapy efficacy and genetic abnormalities with signatures. About 48 individuals who qualified were enrolled between December 2019 and December 2020. The ORR was 45.9% (95% CI, 31.4%-60.8%) at a median follow-up of 17.6 months. Median progression-free survival (PFS) was 9.1 months (95% CI, 5.8-9.6), and median overall survival (OS) was 19.2 months (95% CI, 11.6-not reached). Fatigue (14.6%) and skin rash (10.4%) were the only treatment-related adverse events (AEs) of grades 3/4 that were less than 10%. Overall, 18 patients (35.4%) suffered from immune-related AEs, although no deaths were attributed to the treatment. Prolonged median PFS was predicted solely by a high tumor mutational burden (TMB-H; top 20%; ≥7.1 mut/Mb) but not by a high TMB. Patients with loss-of-function mutations in chromatin remodeling genes had a significantly longer median PFS and OS than those without changes in up to 28.9% of cases. When it comes to ABTC, NGS is a promising and risk-free treatment option. Possible predictive utility of using a surrogate biomarker: impaired functioning of chromatin remodeling genes.
