<p>Efficacy and safety of nivolumab for metastatic biliary tract cancer</p>

Abstract

ObjectivePD-1 inhibitors have improved efficacy in many cancers. There are currently no reports of the use of PD-1 inhibitors, such as nivolumab, for metastatic biliary tract cancer (mBTC). This study reviewed the efficacy and safety of nivolumab for mBTC with the aim of exploring ways to improve efficacy and survival.MethodsThirty patients with mBTC were voluntarily treated with nivolumab at the PLA General Hospital. Nivolumab 3 mg/kg was administered. Progression-free survival (PFS) and overall survival were evaluated by Kaplan–Meier and univariate and multivariate analyses were carried out for clinical characteristics. Objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs) were also evaluated.ResultsThe median treatment cycle is four cycles. One case was complete response, 5 cases partial response, 12 cases stable, and 12 cases progression. ORR was 20%, DCR was 60%, and PFS was 3.1 months (95% CI: 2.13–4.06). The AEs of nivolumab monotherapy were fatigue (three cases), fever (two cases), hypothyroidism (one case), skin reaction (one case), and liver injury (one case). Nivolumab combined with chemotherapy related grade 1–2 hematologic toxicity were leukopenia (five cases) and thrombocytopenia (two cases), and grade 3–4 were leukopenia (three cases). Non-hematologic toxicity grade 1–2 were nausea and vomiting (four cases), fatigue (four cases), fever (three cases), peripheral neurotoxicity (three cases), and hypothyroidism (one case). Univariate analysis showed that PFS of nivolumab combined with chemotherapy was statistically significant compared with that of nivolumab monotherapy (4.1 vs 2.3 months, P=0.031). Programmed death-ligand 1 (PD-L1) expression positively has no relationship with better PFS in contrast with PD-L1 negatively (3.6 vs 3.0 months P>0.05). Multivariate analysis show nivolumab combined with chemotherapy was only the independent factor for longer PFS (HR: 0.432, P<0.05).ConclusionThe safety of nivolumab in mBTC is controllable. Further selection of superior populations is needed to improve the efficacy of nivolumab in mBTC.

Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE‐158 and KEYNOTE‐028 studies

“…Overall, in advanced BTC, additional analyses are needed to identify predictive biomarkers. received nivolumab as second-line therapy or later) 22. Among all 30 patients, ORR was 20.0% and median PFS was 3.1 (95% CI, 2.13-4.06) months; PFS was unaffected by PD-L1 expression (P = .801) 22.…”

Immunotherapy in Gastrointestinal Cancers

“…However, in a subgroup of patients with MSI-H PDAC (n = 22), the median OS was 4 months with a median PFS of only 2.3 months. Thus, despite their MSI-H status, these patients do not seem to have a major benefit from checkpoint inhibitors [33].…”

“…ORR was 17.4% [34]. In another study, nivolumab treatment showed an ORR of 20% in all patients with metastatic biliary tract cancer, independently of the PD-L1 status of the tumor [35]. In dMMR biliary tract cancers, pembrolizumab achieved an ORR of 53% in a phase II study [1].…”

Systemic therapy for advanced cholangiocarcinoma: new options on the horizon

“…The PD-1 inhibitor nivolumab has also been evaluated in patients with biliary tract cancer. In a study of 30 patients with metastatic disease, nivolumab was associated with an ORR of 20% and a disease control rate of 60%; the median PFS was 3.1 months [85] . Preliminary results of an ongoing phase II trial in patients with advanced refractory biliary tract cancer indicate an ORR of 22%, with a disease control rate of 60%.…”