Reactive capillary hemangiomas: a novel dermatologic toxicity following anti-PD-1 treatment with SHR-1210

Chen, Xuelian; Ma, Lifang; Wu, Xi; Mo, Hongnan; Wu, Dawei; Lan, Bo; Dong, Qiu‐Ting; Zhang, Hongtu; Huang, Jing; Xu, Bo

doi:10.20892/j.issn.2095-3941.2018.0172

Cited by 55 publications

(42 citation statements)

References 29 publications

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“…In our pooled analysis, the most common AEs for camrelizumab alone were RCCEP, fatigue, AST increase, proteinuria, and pruritus. RCCEP has been considered as a unique toxicity of camrelizumab treatment (Chen et al, 2019a;Teng et al, 2019), but it has also been reported in 2.4% of patients treated with nivolumab and pembrolizumab for advanced melanoma (Hwang et al, 2016). In our study, RCCEPs occurred in as high as 76.6% of various solid cancer patients, and there was no grade ≥3 RCCEPs.…”

Section: Discussionsupporting

confidence: 43%

“…In our study, RCCEPs occurred in as high as 76.6% of various solid cancer patients, and there was no grade ≥3 RCCEPs. The median time from the camrelizumab treatment to the onset of RCCEP was 2-4 weeks in previous studies (Chen et al, 2019a;Chen et al, 2020a). Most RCCEPs occurred on the skin (mainly on the face and trunk), and a few were found in oral and nasal mucosa.…”

Section: Discussionmentioning

confidence: 85%

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

Wang

et al. 2020

Front. Pharmacol.

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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

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Section: Discussionsupporting

confidence: 43%

Section: Discussionmentioning

confidence: 85%

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

Wang

et al. 2020

Front. Pharmacol.

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“…However, Chinese patients treated with camrelizumab had similar skin toxicities, including similar times from the start of treatment to onset and the disappearances of RCCEP after longer treatment periods, including patients who were still receiving camrelizumab. 11,28 Given these observations, we also cannot exclude that camrelizumab may interact with an unknown ligand. Recent studies have suggested that despite similarities in binding affinity, PD-1 inhibitors are folded differently and this may have subtle implications on their clinical profile.…”

Section: Discussionmentioning

confidence: 99%

<p>A First-in-Human Dose Finding Study of Camrelizumab in Patients with Advanced or Metastatic Cancer in Australia</p>

Lickliter¹,

Gan²,

Voskoboynik³

et al. 2020

DDDT

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Purpose: Camrelizumab inhibits PD-1 in non-clinical models and showed typical non-clinical pharmacokinetic (PK) and safety profiles for an IgG4 monoclonal antibody. We report results from the First-inHuman Phase 1 trial of camrelizumab in Australian population. Methods: Camrelizumab was administered to patients with advanced solid tumors who had failed standard therapies. In the dose-escalation phase (n=23), camrelizumab was administered intravenously at 1 mg/kg, 3 mg/kg, 6 mg/kg, and 10 mg/kg every 2 weeks. In dose expansion (n=26), camrelizumab was given at 200 mg or 600 mg every 4 weeks. Results: Two dose-limiting toxicities were observed during dose escalation: transaminase elevation and diarrhea (both grade 3). Overall, treatment-related adverse events were consistent with the expected toxicity profile of immune checkpoint inhibition, with the striking exception of the dose-related development of angiomatous skin lesions characterized as reactive cutaneous capillary endothelial proliferation. The PK profile showed a doseprogressive increase in half-life from 3 days at 1 mg/kg to 7 days at 10 mg/kg. Moreover, receptor occupancy assays showed a PD-1 occupancy of >50% in most patients out to 28 days post-dose. The objective response rate was 15.2% (95% CI 6.3-28.9). Conclusion: Camrelizumab has manageable toxicity and encouraging preliminary antitumor activity in advanced solid tumors in Australia. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02492789.

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“…Although nearly half of patients presented with any grade of hypertension (47.5%), it was clinically controllable and could be improved by treatment and most manifested with mild symptoms. Similar to the molecular mechanism of camrelizumab which is most frequently characterized by reactive cutaneous capillary endothelial proliferation 32 , 33 , the binding epitope of sintilimab is different from that of other PD-1 immune checkpoint inhibitors. We hypothesize that the reactivation of the immune response by sintilimab may play a key role in interrupting some unknown signalling pathway in the pathogenesis of hypertension.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effectiveness and safety of sintilimab-dominated triple therapy in unresectable hepatocellular carcinoma

Dai

Cai

Mugaanyi

et al. 2021

Sci Rep

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Immune checkpoint inhibitor therapy has shown promising results in patients with unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy. This was a 22 months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n = 22), sintilimab-sorafenib duotherapy (duplex group, n = 23), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n = 35). The principal evaluation criteria were overall survival and progression free survival in the population, assessed according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). Secondary evaluation criteria were safety, objective response rate and disease control rate. From March 1st, 2019 to December 31, 2020, 80 patients with unresectable hepatocellular carcinoma were included and divided into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0 months (95% CI 7.7–14.3). Median overall survival was 13.0 months (95% CI NE–NE), 9.0 months(95% CI 6.3–11.7)and 3.0 months (95% CI 1.9–4.1, p < 0.0001) in the triple therapy, duplex and sintilimab groups respectively, while the corresponding median progression-free survival were 5.0 months (95% CI 2.9–7.1, p < 0.001), 4.0 months (95% CI 2.8–5.2) and 2.0 months (95% CI 1.7–2.3). Disease control and clinical benefits rates were higher in the triple therapy group (80%, 95% CI 63.1–91.6, p < 0.001; 54.3%, 95% CI 36.6–71.2, p < 0.01) compared to the sintilimab group. Median duration of disease control was 4.0 months (95% CI NE–NE, p < 0.01) in the triple therapy group, longer than that of the duplex group (2.0 months, 95% CI 0.9–3.1) and sintilimab group (2.0 months, 95% CI 0.8–3.2). Grade 3 or 4 treatment-related adverse events occurred in 26.3% of 80 patients with hypertension was the most common event observed (38, 47.5%), however, other severe toxic effects were infrequent. Sintilimab combined with sorafenib and transcatheter arterial chemoembolization might have more beneficial effects on overall and progression-free survival and on the duration of disease control outcomes than both sintilimab monotherapy and sintilimab-sorafenib duotherapy in patients with unresectable hepatocellular carcinoma. This triple therapy model might represent an innovative and effective option for inoperable liver cancer.

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Reactive capillary hemangiomas: a novel dermatologic toxicity following anti-PD-1 treatment with SHR-1210

Cited by 55 publications

References 29 publications

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

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

<p>A First-in-Human Dose Finding Study of Camrelizumab in Patients with Advanced or Metastatic Cancer in Australia</p>

Therapeutic effectiveness and safety of sintilimab-dominated triple therapy in unresectable hepatocellular carcinoma

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