Abstract
BackgroundEvidence for the efficacy of immunotherapy in biliary tract cancer (BTC) is limited and unsatisfactory.MethodsChinese BTC patients receiving a PD-1 inhibitor with chemotherapy, PD-1 inhibitor monotherapy or chemotherapy alone were retrospectively analyzed. The primary outcome was overall survival (OS). The key secondary outcomes were progression-free survival (PFS) and safety. Patients previously treated with any agent targeting T cell costimulation or immune checkpoints were excluded.ResultsThe study included 77 patients (a PD-1 inhibitor plus chemotherapy, n = 38; PD-1 inhibitor monotherapy, n = 20; chemotherapy alone, n = 19). The median OS was 14.9 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 4.1 months with PD-1 inhibitor monotherapy (HR 0.37, 95% CI 0.17–0.80, P = 0.001) and the 6.0 months with chemotherapy alone (HR 0.63, 95% CI 0.42–0.94, P = 0.011). The median PFS was 5.1 months with a PD-1 inhibitor plus chemotherapy, significantly longer than the 2.2 months with PD-1 inhibitor monotherapy (HR 0.59, 95% CI 0.31–1.10, P = 0.014) and the 2.4 months with chemotherapy alone (HR 0.61, 95% CI 0.45–0.83, P = 0.003). Grade 3 or 4 treatment-related adverse events were similar between the anti-PD-1 combination group and the chemotherapy alone group (34.2% and 36.8%, respectively).ConclusionsAnti-PD-1 therapy plus chemotherapy is an effective and tolerable approach for advanced BTC.
Highlights
Biliary tract cancer (BTC), which mainly comprises intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder carcinoma (GBC), is an1 3 Vol.:(0123456789)Cancer Immunology, Immunotherapy (2019) 68:1527–1535 invasive heterogeneous malignant tumor [3]
A phase II study examining the efficacy of the antiprogrammed death-1 antibody pembrolizumab in dMMR/microsatellite instability-high (MSI-H) solid tumors showed that two of the four biliary tract cancer (BTC) patients responded to the treatment; this may not be achievable in the general population, as the dMMR/ MSI-H phenotype is only observed in less than 10% BTC patients [12, 13]
The combination of ICIs with lenvatinib moderately increased the objective response rate (ORR) to 21.4% (3/14) in an observational study [15], but this trend was not observed in another phase I trial where pembrolizumab plus ramucirumab induced a response in only 4% of the biomarker-unselected BTC-treated patients and the median progression-free survival (PFS) and median overall survival (OS) were 1.6 months and 6.4 months, respectively
Summary
Biliary tract cancer (BTC), which mainly comprises intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder carcinoma (GBC), is an1 3 Vol.:(0123456789)Cancer Immunology, Immunotherapy (2019) 68:1527–1535 invasive heterogeneous malignant tumor [3]. Surgery provides the only potentially curative treatment for BTC; the majority of cases present with unresectable disease due to the difficulty in obtaining an early diagnosis [6] Chemotherapy such as gemcitabine plus platinum is available as the standard of care for those who suffer from metastatic and/or unresectable BTC, it only confers an objective response rate (ORR) of 20%, a median overall survival (OS) of 6–8 months, and a 5-year survival rate of less than 10% [3, 7,8,9]. The published data have indicated that the frequency of PD-L1-positive BTC is quite low; the rate of PD-L1 positivity (1% of the cutoff value) in cholangiocarcinoma and gallbladder cancer is approximately 5% and 20%, respectively [17, 18] Based on these limited results, the efficacy of ICI alone or in combination with antiangiogenic therapy for BTC is still modest. Conclusions Anti-PD-1 therapy plus chemotherapy is an effective and tolerable approach for advanced BTC
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