Recognizing Prognostic and Predictive Biomarkers in the Treatment of Non-Small Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors (ICIs)

Giustini, Nicholas P.; Bazhenova, Lyudmila

doi:10.2147/lctt.s235102

Cited by 17 publications

(12 citation statements)

References 87 publications

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“…Although some authors have reported a predictive and prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in patients with advanced NSCLC undergoing different systemic treatments, its role in NCSLC patients with BMs has yet to be clarified (21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitors With or Without Bone-Targeted Therapy in NSCLC Patients With Bone Metastases and Prognostic Significance of Neutrophil-to-Lymphocyte Ratio

et al. 2021

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IntroductionBone metastases (BMs) are a negative prognostic factor in patients with non-small cell lung cancer (NSCLC). Although immune-checkpoint inhibitors (ICIs) have dramatically changed the therapeutic landscape of NSCLC, little information is available on BMs from NSCLC treated with ICIs alone or in association with bone-targeted therapy (BTT) such as zoledronate or denosumab.MethodsFrom 2014 to 2020, 111 of the 142 patients with BMs secondary to NSCLC extrapolated from the prospective multicenter Italian BM Database were eligible for analysis. Information on blood count, comorbidities, and toxicity was retrospectively collected. The neutrophil-to-lymphocyte ratio (NLR) pre- and post-treatment was calculated. Survival was analyzed using the Kaplan–Meier method, with statistical significance of survival differences assessed using the log-rank test.ResultsMedian age was 66 (range, 42–84) years. Performance status (PS) Eastern Cooperative Oncology Group (ECOG) was 0–1 in 79/111 patients. The majority of patients (89.2%) had adenocarcinoma histology. At a median follow-up of 47.4 months, median progression-free (mPFS) and overall survival (mOS) was 4.9 (95%CI, 2.8–10.0) and 11.9 (95%CI, 8.2–14.4) months, respectively. Forty-six (43.4%) patients with BM NSCLC underwent first- or further-line therapy with ICIs: 28 (60.8%) received nivolumab, 9 (19.6%) pembrolizumab, and 9 (19.6%) atezolizumab. Of the 46 patients treated with ICIs, 30 (65.2%) underwent BTT: 24 (80.0%) with zoledronate and 6 (20.0%) with denosumab. The ICI-alone group had an mOS of 15.8 months [95%CI, 8.2–not evaluable (NE)] vs. 21.8 months (95%CI, 14.5–not evaluable) for the ICI plus BTT group and 7.5 (95%CI, 6.1–10.9) months for the group receiving other treatments (p < 0.001). NLR ≤5 had a positive impact on OS.ConclusionBTT appears to have a synergistic effect when used in combination with ICIs, improving patient survival.

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Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitors With or Without Bone-Targeted Therapy in NSCLC Patients With Bone Metastases and Prognostic Significance of Neutrophil-to-Lymphocyte Ratio

et al. 2021

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“…However, how to screen the best beneficiaries has always been the focus of immunotherapy research, and the development of biomarkers is one of the major research directions. [ 45 , 46 ] Currently, the ICIs therapy can effectively improve the prognosis of various cancers, and the immune checkpoint expression has become an important indicator of ICIs therapy. [ 47 ] TIDE algorithm is a novel method to predict treatment response to ICIs, which can replace a single biomarker.…”

Section: Discussionmentioning

confidence: 99%

Construction of a pyroptosis-related lncRNAs signature for predicting prognosis and immunotherapy response in glioma

Huang¹,

Yan²,

Jiang³

et al. 2023

Medicine

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Recent studies have proved that pyroptosis-related long non-coding RNAs (PRlncRNAs) are closely linked to tumor progression, prognosis, and immunity. Here, we systematically evaluated the correlation of PRlncRNAs with glioma prognosis. This study included 3 glioma cohorts (The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Gravendeel). Through Pearson correlation analysis, PRlncRNAs were screened from these 3 cohorts. Univariate Cox regression analysis was then carried out to determine the prognostic PRlncRNAs. A pyroptosis-related lncRNAs signature (PRLS) was then built by least absolute shrinkage and selection operator and multivariate Cox analyses. We systematically evaluated the correlation of the PRLS with the prognosis, immune features, and tumor mutation burden in glioma. A total of 14 prognostic PRlncRNAs overlapped in all cohorts and were selected as candidate lncRNAs. Based on The Cancer Genome Atlas cohort, a PRLS containing 7 PRlncRNAs was built. In all cohorts, the PRLS was proved to be a good predictor of glioma prognosis, with a higher risk score related to a poorer prognosis. We observed obvious differences in the immune microenvironment, immune cell infiltration level, and immune checkpoint expression in low- and high-risk subgroups. Compared with low-risk cases, high-risk cases had lower Tumor Immune Dysfunction and Exclusion scores and greater tumor mutation burden, indicating that high-risk cases can be more sensitive to immunotherapy. A nomogram combining PRLS and clinical parameters was constructed, which showed more robust and accurate predictive power. In conclusion, the PRLS is a potentially useful indicator for predicting prognosis and response to immunotherapy in glioma. Our findings may provide a useful insight into clinically individualized treatment strategies for patients.

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“…14 alteration; 9.7 for BRAF mutation; and 10.3 for KRAS mutation ( p < 0.001 in all groups in Wilcoxon signed-rank test vs. KRAS ). Furthermore, high TMB was correlated with high DNA repair deficiency, another candidate for ICIs response predictor [ 58 , 59 ]. Singal et al analysis of the clinogenomic database showed differences regarding TMB among distinct driver mutations.…”

Section: Molecularly Targeted Therapies and Immunotherapeutics In Nsc...mentioning

confidence: 99%

Immunotherapy in Non-Small-Cell Lung Cancer Patients with Driver Alterations: A New Strategy?

Krzyżanowska

Krawczyk

Wojas‐Krawczyk

et al. 2022

Cells

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For many years, researchers have been trying to develop the most effective ways to fight lung cancer, which is the cause of the largest number of cancer-related deaths among men and women worldwide. The most advanced treatments for nearly all non-small-cell lung cancer (NSCLC) types include immunotherapy with immune checkpoint inhibitors (ICIs), mainly anti-programmed death 1/anti-programmed death ligand 1 monoclonal antibodies (anti-PD-1/PD-L1 mAbs) in monotherapy or in combination with other strategies. Despite significant advances, long survival is not achievable in most cases, so new solutions are constantly being sought. One of the questions raised by oncologists is the efficacy of ICIs in patients with molecular driver alterations, especially when the possibilities of using molecularly targeted therapies are exhausted (e.g., due to resistance to tyrosine kinase inhibitors). There are studies investigating this problem, but it is still poorly described. Among probable immunotherapy’ failures reasons, low immunogenicity of tumors with one driver mutation is listed. Nevertheless, in some cases, the therapy is efficient, and more research is required to establish the management of NSCLC patients with oncogenic driver abnormalities. The aim of this article is to review current discoveries in this matter.

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Recognizing Prognostic and Predictive Biomarkers in the Treatment of Non-Small Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors (ICIs)

Cited by 17 publications

References 87 publications

Immune Checkpoint Inhibitors With or Without Bone-Targeted Therapy in NSCLC Patients With Bone Metastases and Prognostic Significance of Neutrophil-to-Lymphocyte Ratio

Immune Checkpoint Inhibitors With or Without Bone-Targeted Therapy in NSCLC Patients With Bone Metastases and Prognostic Significance of Neutrophil-to-Lymphocyte Ratio

Construction of a pyroptosis-related lncRNAs signature for predicting prognosis and immunotherapy response in glioma

Immunotherapy in Non-Small-Cell Lung Cancer Patients with Driver Alterations: A New Strategy?

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