The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers

Abstract

Background: Camrelizumab (SHR1210) is a high-affinity, humanized immunoglobulin programmed cell death 1 (PD-1) monoclonal antibody. It was developed by Jiangsu Hengrui Medicine Co. Ltd. and has been approved for relapsed or refractory classical Hodgkin lymphoma patients and hepatocellular carcinoma patients in China. Apatinib is an orally administered vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and has been approved for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in China. Camrelizumab alone and its combination with apatinib have been used in the treatment of various solid cancers. Methods: We searched Embase, PubMed, and other databases with the keyword "camrelizumab" or "SHR1210," and evaluated the safety and efficacy data of the involved studies. Adverse events (AEs) mentioned in at least two studies were summarized, including any grade and grade ≥3 treatment-related AEs. Meanwhile, efficacy data were collected, such as overall response rate (ORR), disease control rate (DCR), duration of response, 6-month progression-free survival (PFS) rate, median PFS time, 12-month overall survival rate, and median overall survival time. Results: The major AEs of camrelizumab alone were reactive cutaneous capillary endothelial proliferation, fatigue, aspartate aminotransferase increase, proteinuria, pruritus, and alanine transaminase increase. The ORR and DCR were 20.2% (95% CI: 15.1-26.6%, p 0.000, I 2 70.360) and 45.8% (95% CI: 39.0-52.7%, p 0.256, I 2 58.661), respectively. In the three studies of combination therapy, two studies were combined with apatinib and one combined with chemotherapy. For these studies, common AEs were hypertension, platelet count decrease, nausea, proteinuria, aspartate aminotransferase increase, and white blood cell count decrease. The pooled

Reactive cutaneous capillary endothelial proliferation following camrelizumab monotherapy or combination therapy for multi-cancers: a large-scale pooled analysis of 10 studies in China

“… 13 , 15 , 25 , 27 , 34 , 37 The mechanism by which camrelizumab causes RCCEP is not fully understood. When combined with the antiangiogenic agent apatinib, the incidence was substantially lower (23.6%) compared with camrelizumab alone, in line with the findings in other studies of camrelizumab plus apatinib 22 , 28 , 29 or another antiangiogenic agent famitinib. 31 , 32 Our previous immunohistochemical analysis found strong capillary endothelial cell staining (CD31) in the dermis, as well as markedly high expressions of endothelial cell proliferation markers (Ki-67) and vascular endothelial growth factor-A (VEGF-A) in the lesion tissues, indicating activation of VEGFR2 signaling.…”

“…Previous reports from individual clinical trials mainly presented the incidence of RCCEP following treatment with camrelizumab alone or in combination. 6 , 13 – 16 , 18 – 40 There is a lack of systematic reporting on clinical characteristics of RCCEP, such as time to onset, duration, and remission data, especially in patients treated with a camrelizumab combination. Similarly, the correlation between RCCEP and efficacy was analyzed from individual clinical studies.…”

Antitumor activity and safety of camrelizumab combined with apatinib in patients with relapsed or refractory peripheral T-cell lymphoma: An open-label, multicenter, phase II study

“…This suggests that antiangiogenic agents may have the ability to improve immunosuppression. Currently, numerous clinical studies have demonstrated the promising antitumor effects of combining ICIs with antiangiogenic agents in various solid tumors, such as lung cancer, hepatocellular carcinoma, colon adenocarcinoma, gastric cancer, melanoma, renal cell carcinoma, and breast cancer ( 31 – 33 ).…”