Abstract
Pembrolizumab, an anti-programmed cell death (PD)-1 monoclonal antibody, is an anticancer agent showing substantial benefit in lung cancer and melanoma treatment. Biliary tract cancer (BTC) has been shown to respond to pembrolizumab; however, no credible data of such treatment outcomes exist. Therefore, we assessed the clinical outcomes and safety of pembrolizumab in patients with gemcitabine/cisplatin-refractory BTC. In this multicenter study, we retrospectively analyzed 51 patients with programmed cell death 1-ligand 1 (PD-L1)-positive gemcitabine/cisplatin-refractory BTC treated with pembrolizumab in four tertiary hospitals in Korea. PD-L1 positivity was defined as the expression of PD-L1 in ≥1% of tumor cells based on immunohistochemical staining (22C3, SP263, and E1L3N assays). The median age of the patients was 66 (range, 43–83) years and 29 (56.9%) were male. Extrahepatic cholangiocarcinoma was the most common cancer type (n = 30, 58.8%). Partial response and stable disease were achieved in 5 (9.8%) and 13 (25.5%) patients, respectively. Median progression-free survival and overall survival were 2.1 (95% CI, 1.7–2.4) and 6.9 (95% CI, 5.4–8.3) months, respectively. Overall, 30 (58.8%) patients experienced treatment-related adverse events (AEs). Only four (7.8%) patients experienced grades 3 and 4 AEs. In PD-L1-positive gemcitabine/cisplatin-refractory BTC, pembrolizumab presented durable efficacy, with a 9.8% response rate and manageable toxicity.
Highlights
Biliary tract cancers (BTCs) consist of all tumors originating in the epithelial cells of the bile duct and they are classified into intrahepatic cholangiocarcinoma (CCA), extrahepatic CCA, and gallbladder cancer, according to their anatomical location within the biliary tree
In the present multicenter retrospective study, we investigated the clinical outcomes and safety profile of pembrolizumab in patients with gemcitabine/cisplatin-refractory BTC using programmed cell death (PD)-L1 positivity as a response biomarker and attempted to identify a subpopulation that would potentially benefit from this treatment
From August 2017 to April 2019, 65 patients with programmed cell death 1-ligand 1 (PD-L1)-positive gemcitabine/cisplatin-refractory BTC who received pembrolizumab were included in this multicenter study with the following inclusion criteria: (1) ≥20 years of age; (2) histologically or cytologically confirmed locally advanced or metastatic BTC; (3) at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [17]; (4) radiologically confirmed presence of progressive disease or intolerance to gemcitabine/cisplatin chemotherapy; (5) ≥1% PD-L1-positive tumor cells as assessed using immunohistochemical (IHC) staining; and (6) receipt of at least one cycle of pembrolizumab
Summary
Biliary tract cancers (BTCs) consist of all tumors originating in the epithelial cells of the bile duct and they are classified into intrahepatic cholangiocarcinoma (CCA), extrahepatic CCA (including perihilar and distal CCA), and gallbladder cancer, according to their anatomical location within the biliary tree. More than 90% of BTCs are adenocarcinoma. The incidence of BTC is the highest in East and South Asia and parts of South America, its global incidence has been increasing significantly [1,2]. Surgical resection is regarded as the curative treatment option for patients with BTC but most patients are not considered suitable candidates for surgery because of an advanced disease status at diagnosis [3,4]. Patients with advanced BTC have a poor prognosis with a dismal survival time of
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