Hyperprogressive disease after immune checkpoint inhibitor therapy in a patient with non‑small cell lung cancer who harbors a TGFBR2 mutation: A case report

Wang, Xiaofang; Xiao, Mei; Li, Teng; Li, Chengcheng

doi:10.3892/etm.2023.11927

Cited by 4 publications

(2 citation statements)

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“…It has been reported that HPD occurs more frequently in patients receiving monotherapy with PD-1 and PD-L1 inhibitors compared to those treated with immunotherapy combined with chemotherapy in NSCLC (17.6% vs. 2.9%, p=0.031) (23). Furthermore, it has been suggested that combining chemotherapy and immunotherapy may be effective in preventing HPD as chemotherapy may synergize with immunotherapy to enhance the anti-tumor effect (24,25). Two factors were found to be associated with HPD.…”

Section: Discussionmentioning

confidence: 99%

Redefining Clinical Hyperprogression: the Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy

Djunadi,

Oh,

Lee

et al. 2024

Preprint

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IntroductionImmune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival.MethodsClinical and radiologic data from 121 non-small cell lung cancer (NSCLC) patients with 136 immunotherapy cases were reviewed retrospectively. Three HPD definitions (Champiat et al., HPDc; Saâda-Bouzid et al., HPDs; and Ferrara et al., HPDf) were employed. Additionally, all new measurable lesions on the post-treatment CT scan were incorporated in measuring the sum of longest diameters (SLD) to define modified HPD (mHPD).ResultsAmong the 121 patients, 4 (3.3%) had HPDc, 11 (9.1%) had HPDs, and none had HPDf. Adding all new measurable lesions increased HPD incidence by 5%–10% across definitions. Multivariate analysis revealed significantly lower progression-free survival (PFS) and overall survival (OS) for patients with HPDc (HR 5.25, p=0.001; HR 3.75, p=0.015) and HPDs (HR 3.74, p<0.001; HR 3.46, p<0.001) compared to those without. Patients with mHPD showed similarly poor survival outcomes as HPD patients. Liver metastasis at diagnosis was associated with HPDs, and a high tumor burden correlated with HPDc.ConclusionsThe incidence and risk factors of HPD varied with different definitions, but mHPD identified more cases with poor outcomes. This comprehensive approach may enhance the identification of at-risk patients and lead to a better understanding of HPD in lung cancer during immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Redefining Clinical Hyperprogression: the Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy

Djunadi,

Oh,

Lee

et al. 2024

Preprint

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“…Subsequently, we also reported a case in which a lung cancer patient with a TGFBR2 mutation experienced hyper‐progression after receiving ICI monotherapy. 10 These findings suggest that the biomarkers discovered by IMPACT may be validated in the clinic, which shows the potential value of IMPACT in biomarker exploration.…”

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confidence: 83%

IMPACT: A web server for exploring immunotherapeutic predictive and cancer prognostic biomarkers

Liu,

Zhang,

Xie

et al. 2023

Clinical & Translational Med

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Dear Editor,Identifying reliable biomarkers for immune checkpoint inhibitors (ICIs) can efficiently screen beneficiaries to improve their clinical use. We developed a public web server, IMPACT, to facilitate the comprehensive investigation of predictive or prognostic biomarkers, interaction effects and biological mechanisms with both public and inhouse datasets (http://www.brimpact.cn/ or http://impact. brbiotech.com/) (Figure 1A).ICIs have heralded a new era in cancer treatment, while most ICI biomarkers have low generalisation performance due to limited data and statistical methods. Currently, several public database-based tools are available to explore potential biomarkers, such as CAMOIP, 1 Cancer-Immu, 2 CRI-iAtlas 3 and cBioPortal. 4 Compared with these tools (Figure 1B and Table S1), IMPACT uniquely allows users to define customised biomarkers by selecting mutation variant types and automatically screening cut-points for continuous biomarkers and any mutation or co-mutation in a gene set and to conduct more rigorous key analyses including customised multivariable, subgroup and interaction analyses in more datasets (Table S2). Here, we illustrate how to use IMPACT to comprehensively explore biomarkers.Users can start by understanding the general performance of a biomarker using PredExplore and ProgExplore modules to analyse the association between gene alteration and survival across all the ICI and non-ICI datasets. Detailed results in each dataset and forest plot of metaanalysis can be automatically generated. Especially, these modules allow users to automatically explore a predictive or prognostic value of any mutation or co-mutation in a gene set. As a case of DNA damage response (DDR) pathway alteration (Figures 2A,B and S1A,B), the results suggest that pathway mutation could accumulate the minimal effect of single DDR gene mutation to observe a significant association with prolonged survival to ICIs. Comutation is usually used to explore synergistic or mutually exclusive effects between genes. The co-mutation analysisThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Cisplatin/gemcitabine/nivolumab

2023

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Hyperprogressive disease after immune checkpoint inhibitor therapy in a patient with non‑small cell lung cancer who harbors a TGFBR2 mutation: A case report

Cited by 4 publications

References 23 publications

Redefining Clinical Hyperprogression: the Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy

Redefining Clinical Hyperprogression: the Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy

IMPACT: A web server for exploring immunotherapeutic predictive and cancer prognostic biomarkers

Cisplatin/gemcitabine/nivolumab

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