PMC8770537_01
Case summary. (A) Summary of disease course, treatment procedure, and key molecular findings. PR, partial response; CR, complete response; PD, progressive disease; mo, months. (B) H&E, HER2, and PD-L1 staining of the primary tumor and lung metastasis. Scale bars: 25 microm. H&E: hematoxylin and eosin. (C) Detailed molecular alterations of the primary tumor and lung metastasis. FC, fold change; MSS, microsatellite stable; TMB, tumor mutational burden.
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A summary of his treatment history is illustrated in  Figure 1A . Immunohistochemical (IHC) staining was positive for HER2 (3+) and negative for PD-L1 ( Figure 1B ).
(A) Computed tomography and MRI images showing the patient's baseline disease, progression on S-1 plus gemcitabine in the liver metastatic lesion, progression on trastuzumab plus afatinib and capecitabine in the brain and lung metastatic lesions, and response to camrelizumab plus trastuzumab and oxaliplatin in the liver, brain, and lung metastatic lesions. (B) Dynamics of cancer antigen 199 (CA199) (U/ml) levels during the entire disease course.
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In September 2019, this combination therapy was discontinued when new brain metastases and pulmonary progression of disease were noted ( Figure 2A ). The lesions of the lung, liver, and brain completely regressed after five cycles ( Figure 2A ). The patient's CA199, which continued to increase during chemotherapy and HER2-directed therapy, quickly fell into the normal range after the addition of camrelizumab, indicative of response to the combination regime ( Figure 2B ).
The management of camrelizumab-related irAEs with anti-VEGF agent apatinib. Representative images showing irAEs of (A) RCCEP, (B) mucosal membrane and their resolution after apatinib treatment. irAE, immune-related adverse event; RCCEP, reactive cutaneous capillary endothelial proliferation.
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The patient's RCCEP became grade 1 on week 3, and completely regressed on week 6 ( Figure 3A ). Interestingly, the addition of apatinib also led to the complete resolution of an endothelial neovessel-based nodule in the right buccal mucosa, a putative camrelizumab-related irAE ( Figure 3B ).