Recurrent Gallbladder Carcinoma With pMMR/MSS Achieved a Complete Response Following Camrelizumab Combined With Apatinib: A Case Report

Gallbladder carcinoma (GBC) with proficient mismatch repair (pMMR)/microsatellite stable (MSS) is associated with limited response to programmed death-1 (PD-1) inhibitor monotherapy. Limited data of PD-1 blockade combined with anti-angiogenic therapy in GBC are reported. One recurrent GBC patient with pMMR/MSS was treated with camrelizumab plus apatinib. After 4 cycles of combination therapy, the patient achieved a durable complete response with manageable toxicity. The next-generation sequencing and immunohistochemistry analysis showed that tumor mutation burden (TMB) was 7.26 mutants/Mb and PD-L1 expression was 10% (tumor proportion score) and 20% (immune proportion score). This case suggests that camrelizumab in combination with apatinib may be an effective treatment option for GBC patients with pMMR/MSS status, who have moderate expression of TMB and PD-L1. Additionally, TMB and PD-L1 expression may serve as potential biomarkers for predicting PD-1 inhibitor response of GBC. Furthermore, this needs to be verified in future studies.

[1]  I. Wistuba,et al.  Efficacy, Safety and Biomarker Analysis of Combined PD-L1 (Atezolizumab) and VEGF (Bevacizumab) Blockade in Advanced Malignant Peritoneal Mesothelioma. , 2021, Cancer discovery.

[2]  Haitao Zhao,et al.  The Efficacy and Safety of Apatinib Plus Camrelizumab in Patients With Previously Treated Advanced Biliary Tract Cancer: A Prospective Clinical Study , 2021, Frontiers in Oncology.

[3]  Shouhua Wang,et al.  The immunological characteristics of gallbladder carcinoma and advances in immunotherapy practices. , 2021, Bioscience trends.

[4]  P. Wen,et al.  Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma , 2020, Clinical Cancer Research.

[5]  Lifeng Wang,et al.  Camrelizumab Plus Apatinib in Extensive-Stage Small-Cell Lung Cancer (PASSION): A Multicenter, Two-Stage, Phase 2 Trial. , 2020, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[6]  A. Stenzinger,et al.  Tumor Mutational Burden as a Predictive Biomarker in Solid Tumors. , 2020, Cancer discovery.

[7]  Jianming Xu,et al.  Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial , 2020, Clinical Cancer Research.

[8]  Hong Wang,et al.  Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE‐158 and KEYNOTE‐028 studies , 2020, International journal of cancer.

[9]  D. Shen,et al.  Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial , 2020, Journal for ImmunoTherapy of Cancer.

[10]  H. Yao,et al.  Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial , 2020, Journal for immunotherapy of cancer.

[11]  M. Schell,et al.  A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer. , 2020, JAMA oncology.

[12]  Ting Chen,et al.  Safety and efficacy of PD-1 blockade-activated multiple antigen-specific cellular therapy alone or in combination with apatinib in patients with advanced solid tumors: a pooled analysis of two prospective trials , 2019, Cancer Immunology, Immunotherapy.

[13]  Haitao Zhao,et al.  Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies , 2019, Journal of Hematology & Oncology.

[14]  F. Hirsch,et al.  Low-Dose Apatinib Optimizes Tumor Microenvironment and Potentiates Antitumor Effect of PD-1/PD-L1 Blockade in Lung Cancer , 2019, Cancer Immunology Research.

[15]  T A Chan,et al.  Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[16]  C. Shao,et al.  Emerging predictors of the response to the blockade of immune checkpoints in cancer therapy , 2018, Cellular & Molecular Immunology.

[17]  Jing Yan,et al.  Targeting VEGF/VEGFR to Modulate Antitumor Immunity , 2018, Front. Immunol..

[18]  M. Hansmann,et al.  Microsatellite Instability Occurs Rarely in Patients with Cholangiocarcinoma: A Retrospective Study from a German Tertiary Care Hospital , 2018, International journal of molecular sciences.

[19]  S. Ramalingam,et al.  Tumor Mutation Burden: Leading Immunotherapy to the Era of Precision Medicine? , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  A. Blair,et al.  Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future. , 2017, Current problems in cancer.

[21]  M. Hansmann,et al.  PD‐L1 expression in extrahepatic cholangiocarcinoma , 2017, Histopathology.

[22]  A. Luciani,et al.  PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma , 2017, Oncotarget.

[23]  Shoab A. Khan,et al.  Traffic congestion classification using motion vector statistical features , 2013, Other Conferences.

[24]  Dai Fukumura,et al.  Vascular normalization as an emerging strategy to enhance cancer immunotherapy. , 2013, Cancer research.

[25]  R. Jain,et al.  Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy , 2012, Proceedings of the National Academy of Sciences.

[26]  A. Rashid,et al.  K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: a population-based study in China. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.