Biliary tract cancer (BTC) is associated with poor prognosis and lack of effective treatment. As the deregulation of the immune system playing a key role in the pathogenesis of BTC, immunotherapy has emerged as a promising treatment. However, the objective response rate (ORR) of pembrolizumab monotherapy is only 17.4% in programmed death ligand-1 (PD-L1) positive advanced BTSs. Immune checkpoint inhibitors combined with other treatment may be a potential way to improve efficacy, but related evidence is limited. We aimed to evaluate the efficacy and safety of nivolumab/pembrolizumab with chemotherapy or target therapy compared with monotherapy in advanced BTCs.
Advanced BTCs patients treated with PD-1 inhibitors alone or plus chemotherapy or target therapy from Dec 2015 to Oct 2017 were retrospectively screened for eligibility. Patients previously treated with any agent targeting T-cell co-stimulation or checkpoint pathways were excluded. The primary outcome was overall survival (OS). Secondary outcome were progression-free survival (PFS), ORR and safety.
In total, 37 patients were included (monotherapy, n = 15; combination, n = 22). Combination group represented significantly longer OS (median, 8.2 vs 3.6 months, HR 0.47 [0.20-1.10], p = 0.011) and longer PFS (median, 3.9 vs 2.0 months, HR 0.58 [0.28-1.19], p = 0.034) than monotherapy group. The ORR was 22.7% (5/22) in combination group and 6.7% (1/15) in monotherapy group (p = 0.368) though no significant difference was observed. No significant difference in the incidence of grade 3-4 treatment-related adverse events (TRAEs) were detected between groups (p > 0.05). Most common grade 3-4 adverse events were thrombocytopenia (13.6%) and leukopenia (9.1%) in combination group, and thrombocytopenia (6.7%) in monotherapy group.
Combination of anti-PD-1 plus chemotherapy or target therapy is effective and tolerable as first-line or beyond for advanced BTCs. Prospective study with larger sample size is needed in the future to further confirm our results.
Clinical trial identification
Legal entity responsible for the study
Chinese PLA General Hospital.
The National Natural Science Foundation of China (81402552 to YH)
All authors have declared no conflicts of interest.