Cardiovascular Toxicity With PD-1/PD-L1 Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis

Liu, Surui; Gao, Wei; Yan, Ning; Zou, Xiaomeng; Zhang, Weike; Zeng, Liangjie; Liu, Jie

doi:10.3389/fimmu.2022.908173

Cited by 14 publications

(17 citation statements)

References 88 publications

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“…In this study, we also compared the risk of a CTLA-4 inhibitor combined with a PD-1/PD-L1 inhibitor to that with a PD-1/PD-L1 inhibitor alone. However, the incidence of cardiovascular toxicity was not increased with this combination, which was consistent with other trials [47,48]. There are several possible reasons why our results showed that combination therapy did not result in higher cardiovascular toxicity compared with monotherapy.…”

Section: Discussionsupporting

confidence: 91%

Cardiovascular toxicity with CTLA‐4 inhibitors in cancer patients: A meta‐analysis

Liu,

Fu,

Jin

et al. 2024

Cancer Innovation

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BackgroundWith the emergence of cytotoxic T lymphocyte‐associated protein‐4 (CTLA‐4) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA‐4 inhibitors by analyzing reported trials that involved CTLA‐4 inhibitor therapy.MethodsRandomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3–5 cardiac and vascular adverse events. These involved comparisons of CTLA‐4 inhibitors to placebo, CTLA‐4 inhibitors plus chemotherapy to chemotherapy alone, CTLA‐4 inhibitors combined with PD‐1/PD‐L1 inhibitors to PD‐1/PD‐L1 inhibitors alone, and CTLA‐4 inhibitors plus target agent to PD‐1/PD‐L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel‐Haenszel method.ResultsOverall, 20 trials were included. CTLA‐4 inhibitors significantly increased the incidence of all‐grade cardiovascular toxicity (OR = 1.33, 95% CI: 1.00–1.75, p = 0.05). The incidence of all‐grade cardiovascular toxicity increased in malignant tumor patients who received single‐agent CTLA‐4 inhibitors (OR = 1.73, 95% CI: 1.13–2.65, p = 0.01), as well as the incidence rate of grades 3–5 cardiovascular adverse events (OR = 2.00, 95% CI: 1.08–3.70, p = 0.03). Compared with the non‐CTLA‐4 inhibitor group, CTLA‐4 inhibitors plus chemotherapy, PD‐1/PD‐L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3–5 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA‐4 inhibitor, but the data were not statistically significant.ConclusionOur findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA‐4 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA‐4 inhibitors when treating malignancies.

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Section: Discussionsupporting

confidence: 91%

Cardiovascular toxicity with CTLA‐4 inhibitors in cancer patients: A meta‐analysis

Liu,

Fu,

Jin

et al. 2024

Cancer Innovation

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“…Thus, ULCA significantly controls primary tumor growth in both ER/PR + breast cancer and TNBC xenograft mouse models and produces systemically detectable levels of encoded transgene IL-12p70. In previous studies, we detected CAdVEC-derived PD-L1 antibody at treated tumor sites but not in blood samples ( 6 ), suggesting that PD-L1 antibody produced by our CAdVEC will not lead to the systemic toxicities seen in patients systemically infused with immune checkpoint inhibitor (ICI) ( 14 ). To compare the benefits of CAdVEC (combination with OAd and HDAd) with single agents, we evaluated the toxicity, antitumor efficacy, and circulating IL-12p70 levels after low-dose (1 × 10 6 vp) and high-dose (1 × 10 9 vp) injection of single agents in the SUM-159 xenograft model (fig.…”

Section: Resultsmentioning

confidence: 78%

Ultralow-dose binary oncolytic/helper-dependent adenovirus promotes antitumor activity in preclinical and clinical studies

et al. 2023

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We show that a binary oncolytic/helper-dependent adenovirus (CAdVEC) that both lyses tumor cells and locally expresses the proinflammatory cytokine IL-12 and PD-L1 blocking antibody has potent antitumor activity in humanized mouse models. On the basis of these preclinical studies, we treated four patients with a single intratumoral injection of an ultralow dose of CAdVEC (NCT03740256), representing a dose of oncolytic adenovirus more than 100-fold lower than used in previous trials. While CAdVEC caused no significant toxicities, it repolarized the tumor microenvironment with increased infiltration of CD8 T cells. A single administration of CAdVEC was associated with both locoregional and abscopal effects on metastases and, in combination with systemic administration of immune checkpoint antibodies, induced sustained antitumor responses, including one complete and two partial responses. Hence, in both preclinical and clinical studies, CAdVEC is safe and even at extremely low doses is sufficiently potent to induce significant tumor control through oncolysis and immune repolarization.

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“…The different treatment regimens on the risk of dyspnea were presented for 19 incidence of dyspnea when compared with single ICI with moderate evidence of heterogeneity among the studies (I 2 = 41%) (Figure 5).…”

Section: Risk Of Dyspneamentioning

confidence: 99%

“…The different treatment regimens on the risk of pneumothorax were presented for 19 low evidence of heterogeneity among the studies (I 2 = 0% and 0%). Double ICIs (P = 0.99; SMD: 0.99; 95% CI: 0.17, 5.77) did not significantly change the incidence of pneumothorax when compared with single ICI with low evidence of heterogeneity among the studies (I 2 = 0%) (Figure 10).…”

Section: Risk Of Pneumothoraxmentioning

confidence: 99%

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Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials

Liu

Luo²,

Jie³

et al. 2023

Front. Immunol.

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BackgroundIn recent years, immune checkpoint inhibitors (ICIs) had extremely rapid growth in anti-cancer and improved outcomes of many malignancies, specifically lung cancer. However, the incidence of ICIs-related adverse events also raised. Using this meta-analysis, ICIs-related respiratory disorders were investigated in lung cancer patients.MethodsUsing Cochrane Library, Embase, and PubMed databases, we performed an integrated search for randomized controlled trials (RCTs) to compare respiratory disorders among different regimens. The data was prepared with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline, and the quality of included studies was evaluated based on the Cochrane manual.ResultsIn total, 22 RCTs were involved in this meta-analysis. Compared with ICIs, chemotherapy reduced the risk of interstitial lung disease (p = 0.03; SMD: 2.81; 95% CI: 1.08, 7.27), pleural effusion (p = 0.002; SMD: 2.12; 95% CI: 1.32, 3.42), and pneumonitis (p < 0.00001; SMD: 9.23; 95% CI: 4.57, 18.64). ICIs plus chemotherapy could provide a higher probability for patients to suffer pneumonitis than chemotherapy (p = 0.01; SMD: 1.96; 95% CI: 1.17, 3.28). In addition, single ICI brought a lower likelihood for patients suffering pneumonitis than double ICIs (p = 0.004; SMD: 2.17; 95% CI: 1.27, 3.69).ConclusionICIs-based treatment, such as ICIs alone, ICIs plus chemotherapy and double ICIs, can raise the incidences of some respiratory disorders in patients with lung cancer. It suggests that ICIs should be conducted based on a comprehensive consideration to prevent ICIs-related respiratory disorders. To a certain degree, this study might be provided to the clinician as a reference for ICIs practice.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022378901, identifier (CRD42022378901).

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Cardiovascular Toxicity With PD-1/PD-L1 Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis

Cited by 14 publications

References 88 publications

Cardiovascular toxicity with CTLA‐4 inhibitors in cancer patients: A meta‐analysis

Cardiovascular toxicity with CTLA‐4 inhibitors in cancer patients: A meta‐analysis

Ultralow-dose binary oncolytic/helper-dependent adenovirus promotes antitumor activity in preclinical and clinical studies

Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials

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