Systemic Sequential Therapy of CisGem, Tislelizumab, and Lenvatinib for Advanced Intrahepatic Cholangiocarcinoma Conversion Therapy

Abstract

Intrahepatic cholangiocarcinoma (CCA), always diagnosed at an advanced stage in recent years, is of high aggression and poor prognosis. There is no standard treatment beyond first-line chemotherapy and no molecular-targeted agents or immune checkpoint inhibitors approved for advanced intrahepatic CCA. Hence, we firstly report an original therapeutic strategy for a 60-year-old patient diagnosed with intrahepatic CCA categorized as Stage IIIB (T3N1M0) by the American Joint Committee on Cancer staging system. After histopathological examination and next-generation sequencing, the patient was treated with four courses of novel systemic sequential therapy (intravenous gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8; oral lenvatinib 8 mg/day from days 1 to 21; intravenous tislelizumab 200 mg on day 15). Then, the patient achieved partial response and was operated on right hemihepatectomy, cholecystectomy, and abdominal lymph node dissection. Without any perioperative complications, the patient was discharged from our hospital in perfect condition. Thereafter, the patient continued to use this new regimen 1 month after surgery for adjuvant therapy and was confirmed without recurrence when we followed up. In a word, we found an effective therapeutic regimen for preoperative advanced intrahepatic CCA conversion therapy, which may become a new approach in cancer treatment in the future.

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

“…Lenvatinib, as a multi-kinase inhibitor of VEGF receptors 1–3, FGF receptors 1–4, platelet derived growth factor receptor α, KIT, and RET, selectively inhibits tyrosine kinase receptors involved in tumor growth and angiogenesis[ 45 ]. Tislelizumab is a PD-1 monoclonal IgG4 antibody of high affinity that is mainly used in hematological malignancies and advanced solid cancers, which was conditionally approved in China[ 45 ].…”

“…Lenvatinib, as a multi-kinase inhibitor of VEGF receptors 1–3, FGF receptors 1–4, platelet derived growth factor receptor α, KIT, and RET, selectively inhibits tyrosine kinase receptors involved in tumor growth and angiogenesis[ 45 ]. Tislelizumab is a PD-1 monoclonal IgG4 antibody of high affinity that is mainly used in hematological malignancies and advanced solid cancers, which was conditionally approved in China[ 45 ]. Ding et al [ 45 ] reported successful neoadjuvant therapy with gemcitabine/cisplatin/lenvatinib/tislelizumab in patients with advanced intraheptic CCA followed by surgical resection with no recurrence at the 10-month follow-up[ 45 ].…”

Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues

“…Another multicenter phase II clinical trial (NCT05620498) is currently in progress assessing the efficacy of combining Tislelizumab, Lenvatinib, and the GEMOX scheme in potentially resectable advanced BTC conversion therapy. In a recently published case report, sequential perioperative therapy of four cycles of GemCis on days 1 and 8; lenvatinib from day 1 to day 21; and tislelizumab on day 15 was found to be effective and well-tolerated [ 75 ]. The LEAP-005 (NCT03797326) ongoing study is evaluating the efficacy and safety of Lenvatinib plus Pembrolizumab in patients with previously treated advanced solid tumors.…”

Combination Therapies for Advanced Biliary Tract Cancer

“…Two case reports, with treatments including lenvatinib plus sintilimab dual therapy and systemic sequential therapy comprising GemCis, tislelizumab, and lenvatinib, had promising results in patients with advanced intrahepatic CCA. 86,87 These pieces of evidence highlight the need for more trials involving ICIs and targeted therapies to improve patient prognosis.…”