Combining PD-1inhibitor with VEGF inhibitor in chemotherapy of cholangiocarcinoma patient

Cholangiocarcinoma (CCA) is considered as a diverse group of epithelial cancers characterized by poor outcomes. Cholangiocarcinoma can be divided into three types according to the original position: Intrahepatic Cholangiocarcinoma (ICC), Perihilar Cholangiocarcinoma (PCC) and Distal Extrahepatic Tumors (DET). The most promising way to cure cholangiocarcinoma is surgery, including laparoscopic liver resection and open liver resection. However, the post-surgical outcome is less than satisfactory and there is a poor 5-years survival rate of 16.5-48%. Furthermore, more than two-thirds of the patients are unable to be treated with surgery when diagnosed with cholangiocarcinoma. According to the present meta-analyses, HBV and HCV infections significantly increase the risk of cholangiocarcinoma. For instance, with the high HBV infection rates in Asia and China, the incidence rate of cholangiocarcinoma is approximately 7 per 1 million people in China. Unfortunately, there are no effective biomarkers and typical clinical features for the early diagnosis of cholangiocarcinoma. Additionally, its poor response and limited chemotherapeutic regimens also render its progression difficult to control. Cholangiocarcinoma's median survival time is commonly less than 24 months after diagnosis and therefore, new therapeutic approaches are strongly needed to improve patients' survival rate. In this article, medical specialists from The Affiliated Brain Hospital of Guangzhou Medical University, China report a case of a male patient with a stage 4 intrahepatic cholangiocarcinoma, who was unsuccessfully treated with different chemotherapy regimens and who was further treated with a new therapeutic method to restrict the progression of the lesion.

This patient had been diagnosed with intrahepatic cholangiocarcinoma for 2 years and when first discovered in August 2018, metastases were found in the lung and multiple lymph nodes. Medical imaging reasonably doubted that the original lesion was in the bile duct. However, a pathologic biopsy confirmed the result in September 2018. Pathological genetic testing showed alterations in the in TP53 and KRAS genes.

According to the specific medical imaging and pathological results, gemcitabine and nedaplatin were used as a first-line chemotherapy regimen in October 2018. After 6 courses of chemotherapy, the disease was assessed as stable. In the February 2019 follow up period, Apatinib and Tigio were used to maintain the treatment. However, the disease progressed after the next assessment in April 2019. Paclitaxel for Injection (Albumin Bound) and Oxaliplatin were used with the expectation of stopping the disease progression. After 2 courses, medical imaging that was performed in June 2019, showed that the disease was progressing again and with an increased growth of the lung lesion. Therefore, the clinician had to change the patient's chemotherapy regimen into Loplat and Retitrexet, which was, unfortunately, unsuccessful after 2 courses. From September 2018 to August 2019, the patient CT images showed that the lung metastases continued to increase, the hepatic lesions were obviously enhanced, and the para-aortic lymph nodes were enlarged and fused. In August 2019, with the absence of a solution, the doctors discussed with other doctors and confirmed the possibility to combine PD-1 and VEGF inhibitors with chemotherapy to control the tumor progression. Therefore, the oncologists recommended the treatment combination of FOLFOX6 (Oxaliplatin 130mg d2 + Calcium Levofolinate 500mg d2 + 5-FU 500mg d2 + 5-FU 3000mg d2 46h; q2w), Camrelizumab (PD-1 inhibitor) (200mg d1) and Fruquintinib (VEGF/VEGFR inhibitor) (5mg d1-21). After discussing this with his family, the patient provided his consent, and consequently, they collected his data for results' comparison.

After a complete course, the liver and lung lesions stopped growing, which was encouraging, but still worrying, and after discussion with the patient, the doctors decided to proceed with the course. Six courses later, they delightfully discovered that the patient's lung lesions were significantly reduced, the liver lesion enhancement was reduced, and the abdominal para-aortic lymph nodes were stable. The lesion was assessed as PR (partial response) and stable afterwards.

Significant efforts have been made in improving survival of cholangiocarcinoma patients. In this case, combining a PD-1 inhibitor, a VEGF/VEGFR inhibitor in chemotherapy for controlling cholangiocarcinoma is a promising therapeutic approach; however, more studies are still needed to fully understand how the treatment works.

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