Neoadjuvant camrelizumab and apatinib combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer: a multicenter randomized phase 2 trial

Lin, Jian-Xian; Tang, Yi-Hui; Zheng, Hua-Long; Ye, Kai; Cai, Jian-Chun; Cai, Li-Sheng; Lin, Wei; Xie, Jian-Wei; Wang, Jia-Bin; Lu, Jun; Chen, Qi-Yue; Cao, Long-Long; Zheng, Chao-Hui; Li, Ping; Huang, Chang-Ming

doi:10.1038/s41467-023-44309-5

Cited by 2 publications

(3 citation statements)

References 87 publications

(86 reference statements)

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“…Apatinib impedes VEGF-driven endothelial cell migration and proliferation, curtailing abnormal vascular growth typical of hemangiomas. However, despite apatinib's efficacy in diminishing skin RCCEP (5,19) in the 2nd case, it did not prevent visceral hemangioma occurrence, underscoring the need for further research to optimize apatinib dosing. Anlotinib (21)(22)(23), an orally administered multi-RTK inhibitor, demonstrates high VEGFR2 inhibitory potency in preclinical trials, akin to apatinib.…”

Section: Discussionmentioning

confidence: 96%

“…In exploring the pathogenic mechanisms of RCCEP, it is highlighted that camrelizumab's binding to VEGFR2 may play a crucial role. Previous studies (5) suggest that RCCEP induced by camrelizumab may be mitigated by the VEGFR2 selective inhibitor, apatinib. However, the administration of bevacizumab in the 1st, 2nd, and 3rd patients did not curtail RCCEP occurrence, owing to bevacizumab's neutralization of VEGF-A and its inability to block VEGFR2 activations instigated by camrelizumab.…”

Section: Discussionmentioning

confidence: 96%

“…Additionally, based on a multicenter phase III clinical trial conducted in 13 countries, the Office of Orphan Products Development (OOPD) of the FDA has awarded Orphan Drug Designation (ODD) to camrelizumab for HCC (4). It also has shown efficacy in gastric cancer (5), cervical cancer (6)(7)(8)(9)(10). The immune-related adverse effect (irAE) of reactive cutaneous capillary endothelial proliferation (RCCEP) occurs in 63.3% (11)-88.6% (12) patients induced by camrelizumab, which is much higher than other PD-1 antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab

Zhang,

Wang,

Liu

et al. 2024

Front. Immunol.

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BackgroundCamrelizumab, a programmed death 1 (PD-1) inhibiting antibody, has demonstrated efficacy in various malignancies and received approval in multiple countries. Despite its therapeutic benefits, camrelizumab is associated with a unique spectrum of immune-related adverse effects (irAEs), predominantly reactive cutaneous capillary endothelial proliferation (RCCEP). However, visceral manifestations of such endothelial proliferations, particularly hepatic cavernous hemangiomas, have not been extensively documented.MethodsThis case series retrospectively reviews six patients who developed hepatic hemangiomas following treatment with camrelizumab in combination with other chemotherapeutic agents. The series highlights the clinical course, imaging findings, management strategies, and outcomes associated with this complication. A detailed analysis was conducted to discern the potential causal relationship between camrelizumab therapy and the development of hepatic hemangiomas.ResultsAll six patients, after varying cycles of camrelizumab-based therapy, presented with hepatic lesions identified as cavernous hemangiomas on imaging. These findings were atypical for metastatic disease and were further complicated by significant clinical events, including massive intra-abdominal bleeding post-biopsy. Discontinuation of camrelizumab led to a reduction in the size of the hemangiomas in two cases, suggesting a potential link between the drug and the development of these vascular lesions. The incidence of RCCEP remained high, and the use of other agents such as bevacizumab did not mitigate the occurrence of hepatic hemangiomas, indicating a possible unique pathogenic mechanism associated with camrelizumab.ConclusionHepatic cavernous hemangioma may represent a rare but clinically significant irAE associated with camrelizumab therapy. This series underscores the importance of vigilant monitoring and a high index of suspicion for atypical hepatic lesions in patients undergoing treatment with PD-1 inhibitors. Further studies are warranted to elucidate the pathophysiology of this complication and to establish guidelines for the management and surveillance of patients receiving camrelizumab.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab

Zhang,

Wang,

Liu

et al. 2024

Front. Immunol.

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Potent therapeutic strategy in gastric cancer with microsatellite instability-high and/or deficient mismatch repair

Ooki,

Osumi,

Yoshino

et al. 2024

Gastric Cancer

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Gastric cancer (GC) is a common malignancy that presents challenges in patient care worldwide. The mismatch repair (MMR) system is a highly conserved DNA repair mechanism that protects genome integrity during replication. Deficient MMR (dMMR) results in an increased accumulation of genetic errors in microsatellite sequences, leading to the development of a microsatellite instability-high (MSI-H) phenotype. Most MSI-H/dMMR GCs arise sporadically, mainly due to MutL homolog 1 (MLH1) epigenetic silencing. Unlike microsatellite-stable (MSS)/proficient MMR (pMMR) GCs, MSI-H/dMMR GCs are relatively rare and represent a distinct subtype with genomic instability, a high somatic mutational burden, favorable immunogenicity, different responses to treatment, and prognosis. dMMR/MSI-H status is a robust predictive biomarker for treatment with immune checkpoint inhibitors (ICIs) due to high neoantigen load, prominent tumor-infiltrating lymphocytes, and programmed cell death ligand 1 (PD-L1) overexpression. However, a subset of MSI-H/dMMR GC patients does not benefit from immunotherapy, highlighting the need for further research into predictive biomarkers and resistance mechanisms. This review provides a comprehensive overview of the clinical, molecular, immunogenic, and therapeutic aspects of MSI-H/dMMR GC, with a focus on the impact of ICIs in immunotherapy and their potential as neoadjuvant therapies. Understanding the complexity and diversity of the molecular and immunological profiles of MSI-H/dMMR GC will drive the development of more effective therapeutic strategies and molecular targets for future precision medicine.

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Neoadjuvant camrelizumab and apatinib combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer: a multicenter randomized phase 2 trial

Cited by 2 publications

References 87 publications

Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab

Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab

Potent therapeutic strategy in gastric cancer with microsatellite instability-high and/or deficient mismatch repair

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