Immune checkpoint inhibitor‐related adverse events in lung cancer: Real‐world incidence and management practices of 1905 patients in <scp>China</scp>

Shi, Yuequan; Fang, Jian; Zhou, Chengzhi; Liu, Anwen; Wang, Yan; Meng, Qingwei; Ding, Cuimin; Ai, Bin; Gu, Yangchun; Yao, Yu; Sun, Huizhen; Guo, Hui; Zhang, Cuiying; Song, Xuejiao; Li, Junling; Xu, Bei; Han, Zhiqiang; Song, Meijun; Tang, Tingyu; Chen, Peifeng; Lü, Hongmin; Shui, Yongjie; Lou, Guangyuan; Zhang, Dongming; Liu, Jia; Liu, Xiangning; Gao, Xing; Zhou, Qing; Chen, Minjiang; Zhao, Jing; Zhong, Wei; Xu, Yan; Wang, Mengzhao

doi:10.1111/1759-7714.14274

Cited by 25 publications

(22 citation statements)

References 40 publications

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“…In a retrospective French cohort of 270 patients the outcomes were also better in patients with irAEs, showing an OS NR vs. 8.21 m, respectively (HR = 0.2); the PFS was 5.2 vs. 1.97 m (HR = 0.42); and ORR was 21.3 vs. 5.7% ( 27 ). Similar data has been observed in an Asian study about patients treated with ICIs in which DFS is higher in the subset of patients who developed toxicity ( 28 ). Other similar series have been published reporting similar outcomes ( 29 , 30 ).…”

Section: Association Between Iraes and Prognosis In Solid Tumorssupporting

confidence: 87%

Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer

Iranzo

Callejo²,

Assaf³

et al. 2022

Front. Med.

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In recent years, immunotherapy-based regimens have been included into the treatment's algorithm of several cancer types. Programmed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) interact with their ligands found on the surface of antigen presenting cells (APC) or tumor cells (PD-L1/2 and CD80/86). Through these interactions, stimulatory or inhibitory signals are established. Immune checkpoint inhibitors (ICIs), block these interactions, and when administered not only as monotherapy but also as part of combination regimens, have shown to improve survival results in multiple advanced cancers leading to an increasing number of patients treated with ICI and, as a consequence, a rise in the number of patients developing immune-related adverse events (irAEs). Presence of irAEs has been associated with greater benefit from treatment, especially when blocking PD-L1. Recent data suggests that treatment benefit persists after discontinuation of ICIs due to a treatment related adverse event, regardless of the grade. Patients experiencing grade 3-4 irAEs are at risk of toxicity recurrence after reintroducing immunotherapy and therefore, the decision to resume the treatment is challenging. In these cases, a multidisciplinary approach is always needed and several factors should be considered. Management of severe toxicities may require systemic corticosteroids which can impact on T-cell function. Due to their immunosuppressive properties, it is necessary to deeper determine how corticosteroids influence responses. In terms of overall survival (OS), the use of steroids as therapy for irAEs seems not to reduce OS and several studies have reported durable responses in patients experiencing autoimmune toxicities treated with corticosteroids.

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Section: Association Between Iraes and Prognosis In Solid Tumorssupporting

confidence: 87%

Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer

Iranzo

Callejo²,

Assaf³

et al. 2022

Front. Med.

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“…The correlation between irAEs and effective was not analyzed in our study due to confounding factors in the real world. However, based on the mechanism of action of ICIs, some published studies have shown that irAEs are associated with substantially improved ORR, DCR, PFS, and OS in patients who were treated with ICIs, and some experts consider irAEs to be a projection of the overall immune response to ICI therapy ( Kobayashi et al, 2020 ; Kotwal et al, 2020 ; Shi et al, 2022 ). A prospective study showed that the development of vitiligo during melanoma treatment increases the likelihood of a positive clinical efficacy ( Hua et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study

Huang

Liu²,

Dong³

et al. 2022

Front. Pharmacol.

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Background & Aims: Immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer treatment, and ICI-related toxicities (i.e., immune-related adverse events (irAEs) have been reported in many clinical studies. However, the toxicity data of real-world have not been fully assessed.Methods: Patients with histologically confirmed solid tumors who had been treated with PD-1 inhibitors were included in the study. Patient data were collected from electronic medical records, including basic characteristics, data of irAEs, management and outcome. Incidences of irAEs were pooled and compared, and the risk of irAEs was also analyzed.Results: A total of 362 solid tumor patients treated with sintilimab (n = 171), camrelizumab (n = 60), toripalimab (n = 72), and pembrolizumab (n = 59) were included. In total, any grade irAEs, grade 1–2 irAEs, and grade ≥3 irAEs accounted for 47.24%, 38.67% and 8.56% of cases, reapectively. Further, 29.24% of patients discontinued immunotherapy due to irAEs, with pneumonitis being the main reason for discontinuation. By comparing the toxicity profiles between different ICIs, we found that reactive capillary haemangiomas were camrelizumab-specific. Additionally, the frequency of irAEs was association with ICIs type, the pooled incidence (standardized rate) of irAEs related to sintilimab, camrelizumab, toripalimab and pembrolizumab were 55.56% (52.81%), 48.33% (55.55%), 33.33% (29.23%) and 38.98% (38.29%), respectively. Sintilimab and camrelizumab had higher incidences of any grade and grade 1–2 than toripalimab (55.56% vs. 33.33%, p = 0.002; 48.54% vs. 25.00%, p = 0.0001) and pembrolizumab (55.56% vs. 38.98%, p = 0.0028; 48.54% vs. 25.42%, p = 0.002), while the grade ≥3 irAEs of pembrolizumab (13.56%) were approximately 1.63- to 1.93-fold higher than other ICIs, and the standardized grade ≥3 of pembrolizumab was significantly higher than that of sintilimab (13.21% vs. 7.12%, p = 0.026), especially for grade ≥3 pneumonitis. Multivariate analysis found that cumulative cycles of ICI (OR = 1.081; 95% CI: 1.023–1.142; p = 0.006), and lung cancer (OR = 1.765; 95% CI: 1.105–2.820; p = 0.017) were independent risk factors for irAEs.Conclusion: The frequency of irAEs is associated with ICI type. The pooled incidence of irAEs related to sintilimab and pneumonitis caused by pembrolizumab were higher. These data indicate the importance of having different monitoring priorities for different PD-1 inhibitors.

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“…A total of 11 studies [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ] included 5404 patients on ICIs, and 101 developed CAEs for an incidence of 0.15–37.78% in which grade 3–5 CAEs accounted for 55.4%. Commonly encountered cardiotoxicities included arrhythmia (32.7%), cardiac-related chest pain (24.8%), elevated cTnI or myocarditis (23.8%), cardiomyopathy (20.8%), pericardial disease (11.9%), and acute coronary syndrome (10.9%).…”

Section: Cardiotoxicity In Different Types Of Cancermentioning

confidence: 99%

ICIs-Related Cardiotoxicity in Different Types of Cancer

Dong

Zhang

et al. 2022

JCDD

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Immune checkpoint inhibitors (ICIs) are rapidly developing immunotherapy cancer drugs that have prolonged patient survival. However, ICIs-related cardiotoxicity has been recognized as a rare, but fatal, consequence. Although there has been extensive research based on different types of ICIs, these studies have not indicated whether cardiotoxicity is specific to a type of cancer. Therefore, we conducted a systematic review to analyze a variety of ICIs-related cardiotoxicity, focusing on different types of cancer. We found that the incidence of ICIs-related cardiac adverse events (CAEs) and common cardiotoxic manifestations vary with cancer type. This inspired us to explore the underlying mechanisms to formulate targeted clinical strategies for maintaining the cardiovascular health of cancer patients.

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Immune checkpoint inhibitor‐related adverse events in lung cancer: Real‐world incidence and management practices of 1905 patients in China

Abstract: Background: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune-related adverse events (irAEs) remain poorly understood, especially in a real-world setting.

Cited by 25 publications

References 40 publications

Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer

Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer

PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study

ICIs-Related Cardiotoxicity in Different Types of Cancer

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