Abstract
Pembrolizumab appears promising for patients with programmed cell death ligand-1 (PD-L1)-positive solid tumors. However, data on immunotherapy for biliary tract cancers (BTC) are limited. We aimed to investigate the predictive value of PD-L1 expression as an immunotherapeutic biomarker in BTC. Patients with advanced BTC (n = 175) were screened for PD-L1 expression using PharmDx assay and microsatellite instability (MSI) status. Of the total of 175 patients, 125 (71%) showed tumoral PD-L1 positivity (≥ 1%) while only two (2/142, 1.4%) showed MSI-High. Among 175 patients, 26 patients were treated with pembrolizumab as a second-line therapy, and tumor response was evaluated. Separating these patients into two groups by PD-L1 expression (high [≥ 50%] vs. low [< 50%]), overall response rate was 23% (56% [5/9] in high PD-L1 group vs. 6% [1/17] in low PD-L1 group, P = 0.004). Disease control rate was also higher in high PD-L1 group (78% vs. 35%, P = 0.019). The six responders showed median progression-free survival of 5.8 months after starting pembrolizumab, and none of them was MSI-High. High PD-L1 expression was associated with a better response to pembrolizumab. PD-L1 expression can potentially serve as an alternative predictive biomarker for pembrolizumab therapy in advanced BTC.
Highlights
Pembrolizumab appears promising for patients with programmed cell death ligand-1 (PD-L1)-positive solid tumors
Predictive biomarkers remain unknown for the vast majority of other tumors; microsatellite instability (MSI) status, tumor-infiltrating lymphocytes (TIL), tumor mutational burden, and several other factors are being investigated as candidate immunotherapeutic biomarkers[14]
Pembrolizumab was recently approved by the Food and Drug Administration for treatment of patients with metastatic or unresectable mismatch repair (MMR)-deficient and/or MSI-High (MSI-H) solid tumors that progressed after prior therapy regardless of tumor type[15]
Summary
Pembrolizumab appears promising for patients with programmed cell death ligand-1 (PD-L1)-positive solid tumors. Patients with advanced BTC (n = 175) were screened for PD-L1 expression using PharmDx assay and microsatellite instability (MSI) status. PD-L1 expression can potentially serve as an alternative predictive biomarker for pembrolizumab therapy in advanced BTC. Interim results of an ongoing trial (KEYNOTE-028, NCT02054806) showed promising outcomes of pembrolizumab (anti-PD-1 antibody) in patients with PD-L1-positive advanced biliary tract c ancers[9]. In several tumors including lung and gastric cancers, PD-L1 expression evaluated by immunohistochemistry (IHC) is used as a crucial biomarker predicting response to anti-PD-1/PD-L1 a gents[11,12]. We evaluated therapeutic response of advanced biliary tract cancer patients to pembrolizumab, and correlated treatment response with biomarkers including PD-L1 IHC
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