Focus on Nivolumab in NSCLC

Cortinovis, Diego; Canova, Stefania; Abbate, Maria Ida; Colonese, Francesca; Bidoli, Paolo

doi:10.3389/fmed.2016.00067

Cited by 7 publications

(4 citation statements)

References 58 publications

(68 reference statements)

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“…Cancers have the ability to disrupt immune response by interfering with adaptive immunity. 3,4 Immunotherapy using immune checkpoint inhibitors, notably anti-PD-1 (programmed cell death protein-1) and anti-PDL-1 (PD1 ligand) antibody, has been shown to improve outcome of stage IIIb/IV NSCLC and is a new standard of care. 5,6 In this setting, pembrolizumab, nivolumab, and atezolizumab have been approved by the Food and Drug Administration FDA and the European Medicines Agency as first-(pembrolizumab) and second-line treatment.…”

Section: Introductionmentioning

confidence: 99%

Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab

Popinat¹,

Cousse

Goldfarb

et al. 2019

OncoImmunology

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Introduction: Our aim was to explore the prognostic value of anthropometric parameters in patients treated with nivolumab for stage IV non-small cell lung cancer (NSCLC). Methods: We retrospectively included 55 patients with NSCLC treated by nivolumab with a pretreatment 18 FDG positron emission tomography coupled with computed tomography (PET/CT). Anthropometric parameters were measured on the CT of PET/CT by in-house software (Anthropometer3D) allowing an automatic multi-slice measurement of Lean Body Mass (LBM), Fat Body Mass (FBM), Muscle Body Mass (MBM), Visceral Fat Mass (VFM) and Sub-cutaneous Fat Mass (SCFM). Clinical and tumor parameters were also retrieved. Receiver operator characteristics (ROC) analysis was performed and overall survival at 1 year was studied using Kaplan-Meier and Cox analysis. Results: FBM and SCFM were highly correlated (ρ = 0.99). In ROC analysis, only FBM, SCFM, VFM, body mass index (BMI) and metabolic tumor volume (MTV) had an area under the curve (AUC) significantly higher than 0.5. In Kaplan-Meier analysis using medians as cutoffs , prognosis was worse for patients with low SCFM (<5.69 kg/m 2 ; p = 0.04, survivors 41% vs 75%). In Cox univariate analysis using continuous values, BMI (HR = 0.84, p= 0.007), SCFM (HR = 0.75, p = 0.003) and FBM (HR = 0.80, p= 0.004) were significant prognostic factors. In multivariate analysis using clinical parameters (age, gender, WHO performance status, number prior regimens) and SCFM, only SCFM was significantly associated with poor survival (HR = 0.75, p = 0.006). Conclusions: SCFM is a significant prognosis factor of stage IV NSCLC treated by nivolumab.

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Section: Introductionmentioning

confidence: 99%

Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab

Popinat¹,

Cousse

Goldfarb

et al. 2019

OncoImmunology

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“…PD-1 expressed on Tregs as well as tumor-associated macrophages, on the other hand, exerts an inhibitory effect on immunity and the anti-tumor effect can be improved by blocking it ( Gordon et al, 2017 ; Overacre-Delgoffe et al, 2017 ). Nivolumab is the first PD-1 blocking mAb for the treatment of NSCLC, which significantly improves objective remission rate and overall survival compared with traditional chemotherapy ( Borghaei et al, 2015 ), especially in patients with PD-L1 expression ≥50% in cancer cells, so nivolumab was approved by the FDA in 2015 for the treatment of metastatic NSCLC ( Cortinovis et al, 2016 ) ( Table 1 ). Pembrolizumab (Keytruda) is a humanized IgG4 anti-PD-1 mAb with no ADCC and CDC effects, and therefore is not cytotoxic.…”

Section: Targetsmentioning

confidence: 99%

Current status of immunotherapy for non-small cell lung cancer

et al. 2022

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Nowadays, lung cancer is still the deadliest oncological disease in the world. Among them, non-small cell lung cancer (NSCLC) accounts for 80%∼85% of all lung cancers, and its 5-year survival rate is less than 15%, making the situation critical. In the past decades, despite some clinical advances in conventional treatments, the overall survival rate of NSCLC is still not optimistic due to its unique physiological conditions and the frequent occurrence of tumor escape. In recent years, immunotherapy has become a new hot spot in lung cancer research, including antibody therapy and cell therapy, which have been developed and utilized one after another, especially immune checkpoint inhibitor (ICI). These approaches have effectively improved the overall survival rate and objective response rate of NSCLC patients by enhancing the immune capacity of the body and targeting tumor cells more effectively, which is more specific and less toxic compared with conventional chemotherapy, and providing more strategies for NSCLC treatment. In this paper, we reviewed the relevant targets, clinical progress and adverse reaction in monoclonal antibodies, antibody-drug conjugates, ICI, bispecific antibodies, T-cell receptor engineered T cell therapy (TCR-T), Chimeric antigen receptor T-cell immunotherapy (CAR-T), and also report on their combination therapy from the immune-related background to provide better NSCLC treatment and prospective.

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“…The combination of PD-1 with its ligand, the programmed cell death protein ligand 1 (PD-L1), which expresses on cancer cells in the tumor microenvironment (TME), will pass on regulatory signals to effector T cells causing T cell exhaustion and antiapoptotic signals to tumor cells resulting in tumor survival, hence severely suppressing the immune response. So far, More than 10 antibodies have been granted for therapy in multiple tumors 8 , and over 1000 clinical trials are being implemented targeting the PD-1/PD-L1 axis 9 , for example, in melanoma 10 , breast cancer 11 , 12 , genitourinary carcinoma 13 , 14 , head and neck cancer 15 , hepatocellular carcinoma 16 , non-small cell lung cancer (NSCLC) 17 , 18 , etc., clearly showing the considerable value of anti-PD-1/anti-PD-L1 therapy. However, only a small fraction of people could benefit from the therapy, partially due to the primary or acquired resistance of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy

Yin¹,

Chen²,

Chen³

et al. 2023

Theranostics

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Immunotherapy has achieved great success recently and opened a new avenue for anti-tumor treatment. Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) are typical immune checkpoints that transmit coinhibitory signals, muting the host immunity. Monoclonal antibodies that block PD-1/PD-L1 axis have benefited many patients with different tumor diseases. However, the objective response rate is still unsatisfactory. In this review, we summarize three strategies targeting PD-L1 based on different forms of PD-L1 and various regulating mechanisms to enhance the therapeutic effect, including blockade of the interaction between PD-L1 and PD-1, downregulation of PD-L1 expression and degradation of mature PD-L1. Thereinto, we describe a variety of materials have been designed to target PD-L1, including antibodies, nanoparticle, peptide, aptamer, RNA, and small molecule. Additionally, we list the drugs with PD-L1 regulation capacity used in clinical and ongoing studies to explore other alternatives for targeting PD-L1 besides anti-PD-L1 monoclonal antibodies. Moreover, we discuss associated opportunities for cancer combination therapy with other modalities such as chemotherapy, radiotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), as these conventional or emerging modalities are capable of increasing the immune response of tumor cells by altering the tumor microenvironment (TME), and would display synergistic effect. At last, we give a brief summary and outlook regarding the research status and future prospect of immunotherapy.

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Focus on Nivolumab in NSCLC

Cited by 7 publications

References 58 publications

Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab

Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab

Current status of immunotherapy for non-small cell lung cancer

Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy

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