Severe immune-related adverse events of immune checkpoint inhibitors for advanced non-small cell lung cancer: a network meta-analysis of randomized clinical trials

Gu, Jingjing; Shi, Lei; Jiang, Xiaowen; Wen, Jing; Zheng, Xiaoming; Hu, Cai; Zhang, Weidong

doi:10.1007/s00262-022-03140-5

Cited by 15 publications

(19 citation statements)

References 54 publications

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“…Moreover, Khoja et al posited that pneumonia and hypothyroidism were complications more commonly observed in the context of PD-1 checkpoint blockade as compared to CTLA-4 checkpoint blockade (62). Zhang et al additionally detected an increase in the risk of pneumonia in individuals undergoing pembrolizumab treatment, while nivolumab was associated with a greater risk of hypothyroidism (63,64). Our results are consistent with these prior findings, as pembrolizumab + chemotherapy and nivolumab + chemotherapy were the most common respective causes of pneumonia and hypothyroidism.…”

Section: Discussionsupporting

confidence: 92%

“…Zhang et al. additionally detected an increase in the risk of pneumonia in individuals undergoing pembrolizumab treatment, while nivolumab was associated with a greater risk of hypothyroidism ( 63 , 64 ). Our results are consistent with these prior findings, as pembrolizumab + chemotherapy and nivolumab + chemotherapy were the most common respective causes of pneumonia and hypothyroidism.…”

Section: Discussionmentioning

confidence: 98%

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The safety of combining immune checkpoint inhibitors and platinum-based chemotherapy for the treatment of solid tumors: A systematic review and network meta-analysis

et al. 2023

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ObjectiveCombination treatment regimens consisting of both immune checkpoint inhibitors (ICI) and chemotherapeutic agents have emerged as the standard of care for a range of cancers. This network meta-analysis (NMA) examined the toxicity profiles and safety rankings of these different ICI-based combination regimens.MethodsThe PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for all randomized controlled trials (RCTs) published as of March 1, 2022 comparing two or more treatment regimens in which at least one arm was comprised of an ICI + platinum-based chemotherapeutic regimen. Treatment-related adverse events (AEs) of any grade and AEs of grade 3 or higher were the primary endpoints for this analysis, while specific AE types were secondary endpoints. This NMA combined both direct and indirect comparisons when analyzing odds ratios (ORs) and the surface under the cumulative ranking curve (SUCRA) for different ICI-based treatment regimens.ResultsIn total, 33 RCTs enrolling 19,012 cancer patients were included in this NMA. Of the analyzed regimens, avelumab + chemotherapy and camrelizumab + chemotherapy were associated with a significantly greater risk of AEs of any grade relative to ipilimumab + chemotherapy, durvalumab + chemotherapy, or pembrolizumab + chemotherapy. No significant differences in the risk of AEs of grade 3 or higher were observed when comparing different ICI regimens. Hepatotoxicity and pyrexia were the most common AEs associated with atezolizumab + chemotherapy treatment. Ipilimumab + chemotherapy was associated with a relatively higher risk of gastrointestinal and skin toxicity. Skin toxicity and hypothyroidism were the major AEs associated with nivolumab + chemotherapy. Fatigue and pneumonia were the most common AEs respectively associated with sugemalimab + chemotherapy and pembrolizumab + chemotherapy regimens.ConclusionsOf the evaluated regimens, camrelizumab + chemotherapy and avelumab + chemotherapy were associated with significantly higher rates of AEs of any grade, whereas durvalumab and sintilimab were relatively safe PD-L1 and PD-1 inhibitors, respectively, when administered in combination with platinum-based chemotherapy. However, none of the evaluated ICI + chemotherapy regimens exhibited any differences with respect to the incidence of grade 3 or higher AEs, offering guidance that may be of value in routine clinical practice.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 98%

The safety of combining immune checkpoint inhibitors and platinum-based chemotherapy for the treatment of solid tumors: A systematic review and network meta-analysis

et al. 2023

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“… 19 Another updated NMA involving 14 RCTs further assessed severe irAEs across these ICI agents. 20 These two studies was considered flawed because of the limited number of included trials and omission of ICI agents and specific irAEs, which inevitably led to instability in network construction as well as insufficient evidence for a conclusion. Given these limitations, we previously performed an NMA involving 38 RCTs to compare the risk of irAEs across different ICI-based regimens and found that ICI monotherapy + CT might be a better choice in advanced lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system

et al. 2022

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“…But CTLA-4 has a greater affinity for CD80/CD86. Once CTLA-4 binds to CD80/86, it can reduce the costimulatory signal received by T cells and negatively regulate the immune response [13,17]. As mentioned above, the PD-1/PD-L1 inhibitor is designed to promote immune normalization by blocking the combination of PD-L1 on the surface of tumor cells, along with PD-1 on T cells.…”

Section: Immune Checkpoint Inhibitors Usher In a New Era In Oncologymentioning

confidence: 99%

“…It is also beneficial to restore the immune killing function of T cells and kill tumor cells. The CTLA-4 inhibitor activates TCR by blocking the combination of CTLA-4 and CD80/CD86, resulting in T cells proliferating in large numbers and attacking tumor cells [17].…”

Section: Immune Checkpoint Inhibitors Usher In a New Era In Oncologymentioning

confidence: 99%

Cancer Immunotherapy: Fecal Microbiota Transplantation Brings Light

Zhang

Shi

et al. 2022

Curr. Treat. Options in Oncol.

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Opinion statement Immunotherapy is revolutionizing tumor treatment by activating the immune response to tumors. Among them, immunotherapy represented by immune checkpoint inhibitors is considered to be a milestone in tumor treatment. It has revolutionized the management of advanced malignant tumors by activating T cells, promoting cytotoxic signaling pathways, and killing tumor cells, effectively improving the overall survival of patients. However, resistance to immunotherapy and immune-related adverse events remain challenges for immunotherapy. It has been demonstrated in previous studies that modulating intestinal microbiota can enhance immunotherapy response and reduce complications. Currently, the more mature method for microbiota regulation is fecal microbiota transplantation, which involves transfering a donor’s microbiome to the recipient in the form of capsules or fecal microbiota suspension to restore the richness of the recipient’s intestinal microbiota. In terms of cancer immunotherapy, fecal microbiota transplantation in patients who fail to respond to immune checkpoint inhibitors is expected to produce better prognosis for patients.

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Severe immune-related adverse events of immune checkpoint inhibitors for advanced non-small cell lung cancer: a network meta-analysis of randomized clinical trials

Cited by 15 publications

References 54 publications

The safety of combining immune checkpoint inhibitors and platinum-based chemotherapy for the treatment of solid tumors: A systematic review and network meta-analysis

The safety of combining immune checkpoint inhibitors and platinum-based chemotherapy for the treatment of solid tumors: A systematic review and network meta-analysis

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system

Cancer Immunotherapy: Fecal Microbiota Transplantation Brings Light

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