Abstract 5517: Addition of PD-1 antibody camrelizumab overcame resistance to trastuzumab plus chemotherapy in a HER2-positive, metastatic gallbladder cancer patient
Authors: Yan Dong , Li Xiaomo , Wang Li , Cheng Yurong , Liu Si 
Published: June 2022

Abstract
HER2 amplification/overexpression is a common driver in a variety of cancers including gallbladder cancer (GBC). For patients with metastatic GBC, chemotherapy remains the standard of care with limited efficacy. The combination of HER2 antibody trastuzumab plus chemotherapy is the frontline treatment option for patients with HER2-positive breast/gastric cancer. Recently, this regime also showed antitumor activity in HER2-positive GBC. However, resistance to this regime represents a clinical challenge. Camrelizumab is a novel PD-1 antibody approved for Hodgkin lymphoma and hepatocellular carcinoma in China. Here we presented a HER2-positive metastatic GBC patient who was refractory to trastuzumab plus chemotherapy but experienced significant clinical benefit after the addition of camrelizumab. A 69-year-old male GBC patient was found disease progression in the lung six month after operation, staged IV (T3N0M1). Immunohistochemical (IHC) staining was positive for HER2 (3+) and negative for PD-L1 in both primary and pulmonary lesions. Chemotherapy including S-1 plus gemcitabine, as well as oxaliplatin plus paclitaxel consecutive failed, with a new lesion discovered in the liver. Genomic profiling with a multi-gene NGS panel testing (Onco Panscan࣪, Genetron Health) of the pulmonary lesion showed the presence of TP53 S241Y, ARID2 R273*, EGFR E872K mutations, HER2 amplification (fold change, 8.7), and high tumor mutational burden (TMB 10.33). He was treated with trastuzumab in combination with afatinib and capecitabine. Unfortunately, progressive disease in the lung and brain was observed after two cycles. Due to progression of disease and high TMB of the pulmonary biopsy, also based on the reported activity of PD-1 antibody plus trastuzumab in trastuzumab-resistant, advanced HER2-positive breast cancer, a triplet regime of camrelizumab, trastuzumab, and oxaliplatin was administered. The lesions of the lung, liver, and brain completely regressed after five cycles. From cycle 8 of maintance regime, an anti-angiogenic agent apatinib was added to treat reactive cutaneous capillary endothelial proliferation (RCCEP), the most common immune-related adverse event (irAE) related to camrelizumab, with complete regression after four months. Currently, the patient remains in remission. Our case highlights the potential of immunotherapy in combination with HER2-targeted therapy in HER2-positive GBC. We also demonstrated that immune-related adverse events (irAEs) associated with camrelizumab can be managed with an anti-VEGF agent apatinib. This case not only highlights the importance of irAE management in patients treated with camrelizumab, but also demonstrates the potential of PD-1 antibody plus trastuzumab in HER2-positive GBCs who have developed resistance to chemotherapy and trastuzumab-based targeted therapy.
Citation Format: Dong Yan, Xiaomo Li, Li Wang, Yurong Cheng, Si Liu. Addition of PD-1 antibody camrelizumab overcame resistance to trastuzumab plus chemotherapy in a HER2-positive, metastatic gallbladder cancer patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5517.