Heterogeneous Outcomes of Immune Checkpoint Inhibitor Rechallenge in Patients With NSCLC: A Systematic Review and Meta-Analysis

Xu, Shiting; Shukuya, Takehito; Tamura, Jun; Shimamura, Shoko; Kurokawa, Kana; Miura, Keita; Miyawaki, Taichi; Hayakawa, Daisuke; Asao, Tetsuji; Yamamoto, Keiji; Takahashi, Kazuhisa

doi:10.1016/j.jtocrr.2022.100309

Cited by 15 publications

(18 citation statements)

References 43 publications

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“…While recent studies have shown that rechallenge with ICI after irAE does not significantly improve overall survival 75 , others have concluded that irAEs upon rechallenge display milder toxicities, and suggested that rechallenge might be safe for most patients, depending on the type of irAE 76,77 . Furthermore, a meta-analysis of patients with non-small cell lung cancer rechallenged with ICIs suggests that certain patients with disease progression during ICI discontinuation might benefit from ICI rechallenge 78 . Whether these data are applicable to ICI-related CRS remains to be seen.…”

Section: Discussionmentioning

confidence: 99%

Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: Systematic review of the literature

Liu

Skribek

Harmenberg

et al. 2022

Preprint

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Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events (irAEs). As oncological indications for ICIs widen, their rare side effects become increasingly visible in clinical practice and impact therapy decisions. Here, we provide a systematic review of the literature of CRS and related life-threatening side effects of ICI treatment, such as hemophagocytic lymphohistiocytosis (HLH). We searched Medline, Embase, and the Web of Science Core Collection from inception until October 2021 for reports on CRS, cytokine storm, macrophage activation syndrome, HLH, and related hyperinflammatory disorders in patients with solid cancers receiving ICIs. We found n = 1866 articles, which were assessed for eligibility independently by two examiners. Of those, n = 49 articles reporting on n = 189 individuals were eligible for review. We found that the median time from last infusion to the occurrence of CRS/HLH was approximately nine days, while the onset of symptoms varied from immediately after infusion to one month after treatment. Most patients were treated with either corticosteroids or the anti-interleukin 6 (IL-6) antibody tocilizumab, and although the majority of patients recovered, a few cases were fatal. Concomitant IL-6 and ICI treatment was reported as beneficial for both the antitumoral effect and for limiting side effects. Data from international pharmacovigilance databases underscored that ICI-related CRS and HLH are rare events, but we identified significant differences in reported frequencies, which might suggest substantial underreporting. The results from this first systematic review of CRS/HLH due to ICI therapy highlight that life-threatening systemic inflammatory complications of ICIs are rare and non-fatal in the majority of patients. Limited data support the use of IL-6 inhibitors in combination with ICIs to augment the antitumoral effect and reduce hyperinflammation.

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Section: Discussionmentioning

confidence: 99%

Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: Systematic review of the literature

Liu

Skribek

Harmenberg

et al. 2022

Preprint

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“…This trial excluded cases with SCLC in which the anti‐PD‐L1 antibody drugs atezolizumab 30 and durvalmab, 31 which are currently approved for first‐line induction, were used. However, pembrolizumab, an anti‐PD‐1 antibody drug, may be effective in cases in which anti‐PD‐L1 antibody drugs are ineffective 32,33 . The CGP panel is useful because it adds a new treatment option, pembrolizumab.…”

Section: Discussionmentioning

confidence: 99%

“…However, pembrolizumab, an anti‐PD‐1 antibody drug, may be effective in cases in which anti‐PD‐L1 antibody drugs are ineffective. 32 , 33 The CGP panel is useful because it adds a new treatment option, pembrolizumab. Interestingly, in this study, the CGP panel detected high TMB in 66.7% of cases with SCLC.…”

Section: Discussionmentioning

confidence: 99%

Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single‐center retrospective study

et al. 2022

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Background: The usefulness of comprehensive genomic profiling (CGP) panels for thoracic malignancies after completion of the standard treatment is unclear. Methods: The results of CGP panels for malignant thoracic diseases performed at our hospital between December 2019 and June 2022 were collected. We examined whether CGP panel results led to new treatment, correlated with the effectiveness of immune checkpoint inhibitors (ICIs), or revealed secondary findings related to hereditary tumors. Results: A total of 60 patients were enrolled, of which 52 (86.6%) had lung cancer. In six (10%) patients, the panel results led to treatment with insurance-listed molecular-targeted agents; four patients had EGFR mutations not detected by the real-time polymerase chain reaction assay and two had MET ex.14 skipping mutations. In small-cell lung cancer, the tumor mutation burden was high in 4/6 (66.7%) patients and pembrolizumab was available. Another MET ex.14 skipping mutation was detected in two cases with EGFRtyrosine kinase inhibitor resistance. ICI efficacy was ≤1 year in patients with STK-11, KEAP1, and NEF2L2 mutations. A BRCA2 mutation with a high probability of germline mutation was detected in one patient. A thymic carcinoma with no detectable oncogenic mutation responded to second-line treatment with Tegafur-Gimeracil-Oteracil Potassium (TS-1) for ≥9 years. Conclusions: CGP panels are useful in thoracic malignancies, especially lung cancer, because they can detect overlooked driver mutations and genetic alterations. We believe that the significance of conducting a CGP panel prior to treatment may also exist, as it may lead to the prediction of ICI treatment efficacy.

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“…randomized comparisons are lacking, preliminary evidence from individual cases (34,35) and metaanalyses (36,37) support its safety with low to modest efficacy, e.g. 8-13% ORR in non-small cell lung cancer, depending on the clinical context.…”

Section: Discussionmentioning

confidence: 99%

Immune-based treatment re-challenge in renal cell carcinoma: A systematic review and meta-analysis

et al. 2022

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IntroductionThe use of immune checkpoint inhibitors (ICIs) as a front-line treatment for metastatic renal cell carcinoma (RCC) has significantly improved patient’ outcome. However, little is known about the efficacy or lack thereof of immunotherapy after prior use of anti-PD1/PD-L1 or/and anti-CTLA monoclonal antibodies.MethodsElectronic databases, including PubMed, EMBASE, Medline, Web of Science, and Cochrane Library, were comprehensively searched from inception to July 2022. Objective response rates (ORR), progression-free survival (PFS), and ≥ grade 3 adverse events (AEs) were assessed in the meta-analysis, along with corresponding 95% confidence intervals (CIs) and publication bias.ResultsTen studies which contained a total of 500 patients were included. The pooled ORR was 19% (95% CI: 10, 31), and PFS was 5.6 months (95% CI: 4.1, 7.8). There were ≥ grade 3 AEs noted in 25% of patients (95% CI: 14, 37).ConclusionThis meta-analysis on different second-line ICI-containing therapies in ICI-pretreated mRCC patients supports a modest efficacy and tolerable toxicity.

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Heterogeneous Outcomes of Immune Checkpoint Inhibitor Rechallenge in Patients With NSCLC: A Systematic Review and Meta-Analysis

Cited by 15 publications

References 43 publications

Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: Systematic review of the literature

Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: Systematic review of the literature

Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single‐center retrospective study

Immune-based treatment re-challenge in renal cell carcinoma: A systematic review and meta-analysis

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