Definition, Incidence, and Challenges for Assessment of Hyperprogressive Disease During Cancer Treatment With Immune Checkpoint Inhibitors

Park, Hyo Jung; Kim, Kyung Won; Won, Sang Eun; Yoon, Shinkyo; Chae, Young Kwang; Tirumani, Sree Harsha; Ramaiya, Nikhil H.

doi:10.1001/jamanetworkopen.2021.1136

Cited by 48 publications

(33 citation statements)

References 45 publications

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“…As the nivolumab often had a slow onset of efficacy in realworld practice, and the hyperprogressions made patients had little opportunity to receive the third or fourth line of therapies because of bad general conditions. The hyperprogression has an incidence of 6-43% in ICIs monotherapy and has not been reported in combination therapy of ICIs and chemotherapy [26]. The attempts to combine the nivolumab and chemotherapy in second-line therapy in NSCLC patients are clinically significant.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Wang

Nie

Dai

et al. 2021

Cancer Immunol Immunother

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Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

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Section: Discussionmentioning

confidence: 99%

Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Wang

Nie

Dai

et al. 2021

Cancer Immunol Immunother

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“…Although this should be partially accounted for by a multivariable adjustment in some studies, it was not possible to separate out a pure effect of diabetes from the published studies as no stratified data or analyses were presented. Fourth, publication bias was present in pooling the HR, probably owing to small-study effects [34]. Also, we could not exclude the risk of publication bias against studies reporting negative findings.…”

Section: Discussionmentioning

confidence: 99%

Diabetes As an Independent Risk Factor for Stroke Recurrence in Ischemic Stroke Patients: An Updated Meta-Analysis

Zhang

Wolfe

et al. 2021

Neuroepidemiology

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Introduction: Stroke and its recurrence and diabetes will increase in incidence as the population ages globally. This study explores the relationship between diabetes and stroke recurrence to understand if diabetes is an independent predictor for stroke recurrence in ischemic stroke (IS) patients. Methods: We conducted a systematic review and meta-analysis of studies on the effect of diabetes on stroke recurrence among patients with IS. We searched population-based studies published before 15th February 2021 in PubMed and EMBASE following PRISMA guidelines. Random-effects estimates of the pooled hazard ratio (HR) and 95% confidence intervals (CIs) of each study were generated. A funnel plot and an Egger test were performed to evaluate publication bias. All statistical analyses were conducted in the R software 4.0.1 and Stata 16.0. Results: The search identified 3,121 citations, of which 27 studies met inclusion criteria. Diabetes was associated with a significant risk of stroke recurrence in all IS patients (pooled HR, 1.50; 95% CI: 1.36–1.65; I2 = 61.0%). Similar results were found in lacunar stroke patients with diabetes (pooled HR, 1.65; 95% CI: 1.41–1.92; I2 = 22.0%). Moreover, we found that the risk of recurrent IS among patients of IS with diabetes was higher than that in those without diabetes (pooled HR, 1.53; 95% CI: 1.30–1.81; I2 = 74.0%). Conclusion: Diabetes is an independent risk factor for stroke recurrence among patients with IS.

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“…Kirsten rat sarcoma viral oncogene homolog status is significantly correlated with HPD in colon cancer patients. Two large-scale meta-analyses reported the incidence of HPD in patients with pan-cancer as 1%-30% [21] and 5.9%-43.1% [22] . The clinical prognostic markers used in these analyses were similar to those reported by Chen et al [20] .…”

Section: Incidence and Prognostic Indicators Of Hpdmentioning

confidence: 99%

Mechanism underlying the immune checkpoint inhibitor-induced hyper-progressive state of cancer

Ding¹,

Wen²,

Tong³

et al. 2022

CDR

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Immune checkpoint inhibitors (ICIs) are gradually replacing chemotherapy as the cornerstone of the treatment of advanced malignant tumors because of their long-lasting and significant effect in different tumor types and greatly prolonging the survival time of patients. However, not all patients can respond to ICIs, and even rapid tumor growth after treatment with ICI has been observed in a number of clinical studies. This rapid progression phenomenon is called hyper-progressive disease (HPD). The occurrence of HPD is not uncommon. Past statistics show that the incidence of HPD is 4%-29% in different tumor types, and the progression-free survival and overall survival of patients with HPD are significantly shorter than those of the non-HPD progressor group. With the deepening of the study of HPD, we have established a preliminary understanding of HPD, but the diagnostic criteria of HPD are still not unified, and the addition of biomarkers may break this dilemma. In addition, quite a few immune cells have been found to be involved in the occurrence and development of HPD in the tumor microenvironment, indicating that the molecular mechanism of HPD may be triggered by a variety of ongoing events at the same time. In this review, we summarize past findings, including case reports, clinical trials, and fundamental research; compare the diagnostic criteria, incidence, and clinical prognostic indicators of HPD in different studies; and explore the molecular mechanism and future research direction of HPD.

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Definition, Incidence, and Challenges for Assessment of Hyperprogressive Disease During Cancer Treatment With Immune Checkpoint Inhibitors

Cited by 48 publications

References 45 publications

Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Diabetes As an Independent Risk Factor for Stroke Recurrence in Ischemic Stroke Patients: An Updated Meta-Analysis

Mechanism underlying the immune checkpoint inhibitor-induced hyper-progressive state of cancer

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