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In this case report, we present the case of a 46-year-old woman with a hepatic neuroendocrine tumor (NET G2)-induced liver metastases. Initially, the left lateral lobectomy of the liver was performed. The post-operative pathological examination revealed NET G2, leading to the post-operative recovery with a general review. Further, the re-examination of liver magnetic resonance imaging (MRI) showed post-operative changes in the tumor of the left lateral lobe, with multiple liver masses and possible metastasis. Thus, the liver interventional therapy and apatinib-based targeted therapy based on the "camrelizumab + apatinib" regimen were performed, respectively. The 20-month follow-up indicated a slightly increased hepatic hilum and retroperitoneal lymph nodes, accompanied by hand-foot syndrome. Eventually, the overall condition continued to relieve, indicating that the combined treatment could substantially improve the NET G2 conditions-associated liver metastasis.

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Aims: This study evaluates the safety and preliminary antitumor efficacy of camrelizumab with albumin-binding paclitaxel and cisplatin as first-line therapy for patients with recurrent or metastatic cervical carcinoma. Methods and Material: In this phase 2, open-label, prospective study, 35 patients with recurrent or metastatic cervical carcinoma with no previous systemic chemotherapy were included. The patients were treated with a maximum of six cycles of camrelizumab on day 1, albumin-binding paclitaxel, and carboplatin on day 2, every 3 weeks, followed by camrelizumab once every 3 weeks. The primary outcomes were objective response rate (ORR) and disease control rate (DCR). Secondary outcomes were duration of response (DoR) and safety. Furthermore, 27 patients were included in the per-protocol set for efficacy analysis, whereas for the safety analysis, all patients were included. Results: The median follow-up was 4.53 months, and the complete response, partial response, and stable disease were also achieved in 4 (14.81%), 6 (22.22%), and 13 (48.15%) patients. The ORR and DCR were 40.00% (95% confidence interval: 21.13-61.33%) and 92.00% (73.97-99.01%), respectively. The median DoR was 6.70 months. In addition, the most common adverse events (AEs) were reactive cutaneous capillary endothelial proliferation (RCCEP) (23, 65.71%), gastrointestinal reaction (8, 22.86%), and fever (8, 22.86%). Grade 3 AEs included 5 (14.29%) myelosuppression, and grade 4 AEs included 1 (2.86%) RCCEP and 1 (2.86%) bladder inflammation. Conclusions: Combination therapy of camrelizumab and albumin-bound paclitaxel and carboplatin shows promising efficacy and manageable toxicities in patients with recurrent or metastatic cervical cancer.

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Upper tract urothelial carcinoma (UTUC) is a rare malignant disease, and while locally advanced non-metastatic UTUC can be cured by radical nephroureterectomy (RNU), this procedure leaves patients at high risk of relapse and death from cancer. Though the FDA has currently approved five agents for the systemic immunotherapy treatment of urothelial carcinoma (UC) patients, the effect of immunotherapy in patients with recurrent UTUC still lacks specific evidence. Camrelizumab is a programmed cell death protein 1 (PD-1) inhibitor which has been approved for the treatment of recurrent or refractory classical Hodgkin lymphoma in China and have achieved improvement in a verity of solid tumors with manageable safety profile. We herein report a case of an 80-year-old woman diagnosed with localized UTUC (pT4N0M0) for which she underwent RNU but relapsed after 2 months. As the toxic effects of chemotherapy were intolerable for the patient, she received the PD-1 inhibitor Camrelizumab as a salvage treatment to stop tumor growth. The tumor shrank and the patient achieved partial response (PR) after eight cycles but progressed after 14 cycles. Based on the current evidence, our case indicated that Camrelizumab is a promising agent in treating locally advanced and recurrent UTUC patients with poor performance status and imparted renal function.

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BACKGROUND: PD-1/L1 inhibitor-based immunotherapy is currently under investigation in biliary tract cancer (BTC). Apatinib combined with camrelizumab has achieved promising results in various tumor types. The aim of this study was to assess the safety and efficacy of apatinib plus camrelizumab for advanced biliary tract cancer patients who have received previously treatments. METHODS: This prospective, non-randomized, open-label trial was conducted at Peking Union Medical College Hospital (PUMCH). All included patients received apatinib orally at 250 mg per a day and camrelizumab intravenously at 200 mg every three weeks until disease progression or intolerable toxicity occurred. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1). Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). RESULTS: A total of 22 patients were consecutively enrolled from 1st December, 2018 until 1st August, 2020. Among 21 patients for whom we could conduct efficacy evaluations, no patients achieved a complete response (CR), 4 patients (19%) achieved partial response (PR), and 11 patients had stable disease with a disease control rate of 71.4%. The median overall survival was 13.1 months (95% CI, 8.1-18.2), and the median progression-free survival was 4.4 months (95% CI, 2.4-6.3). All patients experienced treatment related AEs, and grade 3 or 4 AEs occurred in 14 (63.6%) of 22 patients. No treatment related deaths were observed. CONCLUSIONS: This is the first report focusing on the efficacy and safety of camrelizumab plus apatinib in pretreated biliary tract cancer patients. The finding suggests this regimen has favorable therapeutic effects with relatively manageable toxicity. Further trials with a control arm are required to investigate. CLINICAL TRIAL REGISTRATION: identifier NCT04642664.

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Objective: To investigate the safety and efficacy of camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion. Method: Two hundred patients with gastric cancer with serosal invasion who received neoadjuvant therapy from January 2012 to December 2020 were retrospectively analyzed. According to the different neoadjuvant therapy regimens, the patients were divided into the following three groups: the SOX group (S-1 + oxaliplatin) (72 patients), SAP group (S-1 + nab-paclitaxel) (95 patients) and C-SAP group (camrelizumab + S-1 + nab-paclitaxel) (33 patients). Result: The pathological response (TRG 1a/1b) in the C-SAP group (39.4%) was not significantly different from that in the SAP group (26.3%) and was significantly higher than that in the SOX group (18.1%). The rate of ypT0 in the C-SAP group (24.2%) was higher than that in the SAP group (6.3%) and the SOX group (5.6%). The rate of ypN0 in the C-SAP group (66.7%) was also higher than that in the SAP group (38.9%) and the SOX group (36.1%). The rate of pCR in the C-SAP group (21.2%) was higher than that in the SAP group (5.3%) and the SOX group (2.8%). The use of an anti-PD-1 monoclonal antibody was an independent protective factor for TRG grade (1a/1b). The use of camrelizumab did not increase postoperative complications or the adverse effects of neoadjuvant therapy. Conclusion: Camrelizumab combined with nab-paclitaxel plus S-1 could significantly improve the rate of tumor regression grade (TRG 1a/1b) and the rate of pCR in gastric cancer with serosal invasion.

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In the REGONIVO study, regorafenib combined with nivolumab was effective in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC), which indicated anti-angiogenic drugs may enhance the efficacy of immune checkpoint inhibitors. Therefore, we designed a single-arm, single-center, open-label, phase II trial to determine the toxicity and efficacy of SHR-1210 (an anti-PD-1 antibody) plus apatinib in MSS mCRC. The sample size was estimated using a Simon Optimum two-stage design. 10 patients were included at the first stage and if one effective patient observed, an additional 19 patients would be added. Patients with MSS mCRC who refractory to second-line treatment or intolerant to standard treatment were given SHR-1210 200 mg every 2 weeks and apatinib 250-375 mg once daily until unacceptable toxicity or disease progression occurred. In our study, the objective response rate was 0% and the disease control rate was 22.2%. The median progression-free survival was 1.83 months (95% confidence interval (CI) 1.80-1.86 months), and the median overall survival was 7.80 months (95% CI 0-17.07). Treatment-related adverse events (AEs) occurred in all patients (100%). The most common treatment-related AEs were hypertension and proteinuria (70% each). Grade 3 AEs were observed in nine patients (9/10, 90%), and the commonest was hypertension (30%). In conclusion, SHR-1210 combined with apatinib has failed to improve the efficacy of treatment of MSS mCRC, and the intolerable toxicity may be the leading cause.

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The current evidence regarding immunotherapy plus targeted therapy in esophageal neuroendocrine carcinoma (NEC) is lacking. Camrelizumab is a programmed cell death protein 1 inhibitor. Apatinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. A 50-year-old female was initially diagnosed as primary esophageal NEC. Neoadjuvant chemotherapy and Ivor Lewis esophagectomy were performed (ypT3N0M0, stage Ⅱ). Twenty months after the surgery, an isolated mediastinal lymph node recurrence of NEC was recorded. The specimen revealed a positive expression of vascular endothelial growth factor and programmed cell death ligand 1. The diseased lymph node was slightly enlarged after two cycles of first-line paclitaxel liposome and S-1. Second-line apatinib and S-1 for 2 months also resulted in progressive disease. Subsequently, third-line camrelizumab plus apatinib was continued for 5 months. The patient demonstrated a progression-free status for more than 10 months following the combination therapy. Meanwhile, relevant studies of camrelizumab in gastric or esophageal cancer were briefly reviewed. Based on the current evidence, camrelizumab is a promising agent for esophageal cancer. More prospective trials are warranted before a definite recommendation could be drawn.

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WHAT IS KNOWN AND OBJECTIVE: Pulmonary sarcomatoid carcinoma (PSC) is characterized by dismal prognosis and resistance to platinum-based chemotherapy. The immune checkpoint inhibitors showed promising efficacy in the treatment of PSC. Camrelizumab is a programmed cell death protein 1 inhibitor; however, current evidence of its efficacy in PSC is lacking. CASE SUMMARY: A 47-year-old female non-smoker presented with central-type masses in the right upper and lower lobes. PSC (cT4N2M0, stage IIIB) with positive expression of programmed death ligand-1 was diagnosed. First-line camrelizumab plus doxorubicin and cisplatin was introduced, followed by camrelizumab monotherapy due to grade 4 leukopenia and thrombocytopenia during the combination therapy. The lesions indicated a partial remission which endured for more than 20 months. WHAT IS NEW AND CONCLUSION: Camrelizumab plus doxorubicin and cisplatin regimen is a promising option for PSC patients. Further high-quality trials are warranted.

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INTRODUCTION: Camrelizumab (also known as SHR-1210), a humanized monoclonal antibody against PD-1, has been shown to block the binding of PD-1 to PD-L1 and consequently inhibit the immune escape of tumor cells. Recently, camrelizumab was approved as a second-line drug for previously treated advanced hepatocellular carcinoma in China. AREAS COVERED: In this paper, the chemical properties, mechanism of action, pharmacokinetics, clinical efficacy, safety, and tolerability of camrelizumab for the treatment of advanced hepatocellular carcinoma are introduced in detail. The strategy for combination therapy and the potential application of camrelizumab in other solid tumors are briefly described. We performed a systematic review of the literature in PubMed and the following keywords were used: 'SHR-1210,' 'Camrelizumab,' and 'hepatocellular carcinoma.' EXPERT OPINION: Camrelizumab is a selective, humanized, high-affinity IgG4 kappa mAb against PD-1. Camrelizumab showed promising antitumor activity and manageable toxicities and offers a new second-line drug option for patients with advanced hepatocellular carcinoma. Reactive cutaneous capillary endothelial proliferation is a novel but prevalent immune-related dermatologic toxicity of camrelizumab, which is mild, reversible, and predictable. More clinical trials of camrelizumab are ongoing to develop combination therapy strategies and new indications for malignancies.

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PURPOSE: Patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) cancers are prone to response to programmed cell death-1 (PD-1) checkpoint inhibitors. Therefore, we explored the efficacy and safety of a PD-1 checkpoint inhibitor camrelizumab in advanced or metastatic solid tumour with dMMR/MSI-H. METHODS: Patients with dMMR/MSI-H advanced or metastatic solid tumours who had received at least one line of prior systemic chemotherapy were recruited. Camrelizumab was given intravenously 200 mg every 2-week treatment cycle. The primary endpoint was objective response rate according to Response Evaluation Criteria in Solid Tumours v1.1. RESULTS: Twelve patients were enrolled. As data cutoff, eight patients (66.7%, 95% CI 34.9-90.1) achieved objective response. Disease control rate reached 100% (95% CI 73.5-100). Progression-free survival rate at 12 months was 83.3% (95% CI 48.2-95.6), and overall survival rate at 12 months was 90% (95% CI 47.3-98.5). The most common treatment-related adverse events were reactive cutaneous capillary endothelial proliferation (100%), increased alanine aminotransferase (41.7%), and increased aspartate aminotransferase (41.7%). CONCLUSIONS: Camrelizumab provided durable objective response and disease control in pre-treated patients with dMMR/MSI-H advanced or metastatic solid tumour, being a promising treatment option for these patients.

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Objective: To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti- programmed cell death protein-1 (PD-1) antibody, SHR-1210 therapy. Methods: The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR-1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone (ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune-related adrenal insufficiency. Results: Until December 14th, 2018, no SHR-1210 related primary adrenal insufficiency occurred, and the incidence of immune-related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3-4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR-1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR-1210. Conclusions: The incidence of SHR-1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.

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OBJECTIVE: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangiomas (RCHs). Thus we tried to summarize the features of RCHs and estimate their relationship with tumor response. METHODS: This prospective observational study systematically enrolled 98 patients with advanced solid tumors from April 27th, 2016 to June 8th, 2017 in the context of the phase I clinical study of SHR-1210. This report focused on the skin toxicities. Patients underwent entire skin inspection every two weeks while taking medication. The clinical course of RCHs was recorded and their association with tumor response was estimated. The data cut-off date was November 15th, 2017. RESULTS: After a median follow-up of 242 (range, 29-567) days, RCHs were observed in 85.7% (84/98) of patients on cutaneous/mucosal surfaces; 84.5% (71/84) of the RCHs were evaluated as grade 1 adverse events. No grade 3 or 4 RCHs were observed. The time of onset of RCHs was dose dependent and shortest in the 400 mg-dose cohort (P < 0.001). Spontaneous and complete regression of RCHs was observed both during and after treatment. The objective response rate of tumors for patients with RCHs was 28.9% (24/83). However, no responders were observed among the patients without RCHs. CONCLUSIONS: RCHs were prevalent but manageable during treatment with SHR-1210. It might add to the expanding literature regarding immune-related dermatologic adverse events.

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Objective@#To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti- programmed cell death protein-1 (PD-1) antibody, SHR-1210 therapy.@*Methods@#The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR-1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone (ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune-related adrenal insufficiency.@*Results@#Until December 14th, 2018, no SHR-1210 related primary adrenal insufficiency occurred, and the incidence of immune-related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3-4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR-1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR-1210.@*Conclusions@#The incidence of SHR-1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.