Kabir Mody1, Jason Starr1, Michelle Saul2, Kelsey Poorman2, Benjamin A Weinberg3, Mohamed E Salem4, Ari VanderWalde5, Anthony F Shields6. 1. Gastrointestinal Oncology Program, Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA. 2. Caris Life Sciences, Phoenix, AZ, USA. 3. Ruesch Center for The Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA. 4. Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA. 5. West Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Tennessee, Memphis, TN, USA. 6. Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Abstract
BACKGROUND: Patients with biliary tract cancer (BTC) have a dismal prognosis and limited treatment options. Given the potential for immunotherapy in patients with BTC, we studied the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) and evaluated for associated genetic alterations in patients with BTC. METHODS: By immunohistochemistry (IHC), PD-L1 (SP142 antibody; ≥2+ and/or ≥5% staining on tumor cells considered positive) and PD-1 [NAT105 antibody; ≥1+ staining of tumor infiltrating lymphocytes (TILs) considered positive] expression was studied and next-generation sequencing (NGS) was performed using Caris Life Sciences' sequencing panel of 592 genes. A total of 652 patients with BTC were included in this study: 77 extrahepatic cholangiocarcinoma (ECC), 203 gallbladder cancer (GBC), and 372 intrahepatic cholangiocarcinoma (ICC). RESULTS: Of the 652 tumors 8.6% were PD-L1 positive with the following distribution: GBC 12.3% (25/203), ICC 7.3% (27/372), and ECC 5.2% (4/77). There was a statistically significant increase in BRAF, BRCA2, RNF43, and TP53 mutations in PD-L1 positive group as compared to PD-L1 negative. Among other biomarkers tested, TOP2A, tumor mutational burden (TMB) high (≥17 mutations per megabase) (10.7%), and microsatellite instability high (MSI-H) (7.1%) were increased in PD-L1 positive tumors versus PD-L1 negative tumors. CONCLUSIONS: PD-L1 expression was noted in a small percentage (8.6%) of patients with BTC. This finding suggests potential benefit of immunotherapy in this subset of patients. Furthermore, there was a statistically significant association between PD-L1 expression and certain genomic alterations (BRAF, BRCA2, RNF43, TP53) and biomarkers (TOP2A, TMB high, MSI-H), which might direct the use of rational combination strategies and clinical trial development. 2019 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Patients with biliary tract cancer (BTC) have a dismal prognosis and limited treatment options. Given the potential for immunotherapy in patients with BTC, we studied the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) and evaluated for associated genetic alterations in patients with BTC. METHODS: By immunohistochemistry (IHC), PD-L1 (SP142 antibody; ≥2+ and/or ≥5% staining on tumor cells considered positive) and PD-1 [NAT105 antibody; ≥1+ staining of tumor infiltrating lymphocytes (TILs) considered positive] expression was studied and next-generation sequencing (NGS) was performed using Caris Life Sciences' sequencing panel of 592 genes. A total of 652 patients with BTC were included in this study: 77 extrahepatic cholangiocarcinoma (ECC), 203 gallbladder cancer (GBC), and 372 intrahepatic cholangiocarcinoma (ICC). RESULTS: Of the 652 tumors 8.6% were PD-L1 positive with the following distribution: GBC 12.3% (25/203), ICC 7.3% (27/372), and ECC 5.2% (4/77). There was a statistically significant increase in BRAF, BRCA2, RNF43, and TP53 mutations in PD-L1 positive group as compared to PD-L1 negative. Among other biomarkers tested, TOP2A, tumor mutational burden (TMB) high (≥17 mutations per megabase) (10.7%), and microsatellite instability high (MSI-H) (7.1%) were increased in PD-L1 positive tumors versus PD-L1 negative tumors. CONCLUSIONS: PD-L1 expression was noted in a small percentage (8.6%) of patients with BTC. This finding suggests potential benefit of immunotherapy in this subset of patients. Furthermore, there was a statistically significant association between PD-L1 expression and certain genomic alterations (BRAF, BRCA2, RNF43, TP53) and biomarkers (TOP2A, TMB high, MSI-H), which might direct the use of rational combination strategies and clinical trial development. 2019 Journal of Gastrointestinal Oncology. All rights reserved.
Entities:
Keywords:
Cholangiocarcinoma; bile ducts; extrahepatic; gallbladder cancer (GBC); immunotherapy; intrahepatic; mutation
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