First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1

Reck, Martin; Ciuleanu, Tudor; Lee, Jong Seok; Schenker, Michael; Audigier-Valette, Clarisse; Żurawski, Bogdan; Linardou, Helena; Otterson, Gregory A.; Salman, Pamela; Nishio, Makoto; Jimenez, Emmanuel de la Mora; Lesniewski-Kmak, Krysztof; Albert, István; Ahmed, Samreen; Syrigos, Konstantinos; Penrod, John R.; Yuan, Yong; Blum, Steven I.; Nathan, Faith E.; Sun, Xiaowu; Moreno-Koehler, Alejandro; Taylor, Fiona; O’Byrne, Kenneth J.

doi:10.1016/j.jtho.2020.12.019

Cited by 33 publications

(48 citation statements)

References 37 publications

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“…Inflammatory hepatitis is an uncommon cause of treatment interruption in the management of NSCLC with estimates <1% incidence of grade 3 hepatitis and 1%–3% of all grade hepatitis with the use of anti-PD-1/PD-L1 treatment in NSCLC ( 20 , 21 ). The incidence has been shown to increase dramatically with combination therapy and/or the presence of liver metastases ( 10 , 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…Checkpoint inhibitor pneumonitis (CIP) currently occurs in 3%-5% of all cases; however, that estimate rises to 7%-13% in the setting of NSCLC treatment (8). As demonstrated in Checkmate-012, Checkmate-227, and Checkmate-568 (9)(10)(11), this incidence worsens when dual checkpoint inhibitor therapy with anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) is used (12). Furthermore, the increased incidence in NSCLC patients is attributable to the increased association of risk factors for immune-mediated pneumonitis in NSCLC patients including smoking, age >70 years, prior radiotherapy, prior lung disease (including chronic obstructive pulmonary disease), and exposure to the EGFR inhibitor osimertinib (8).…”

Section: Pneumonitismentioning

confidence: 99%

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Management of Immune-Related Adverse Events in Patients With Non-Small Cell Lung Cancer

Burke

Rashdan

2021

Front. Oncol.

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With proven efficacy of the use of immunotherapy in almost all stages of NSCLC, immunotherapy toxicity has become a very important topic that requires immediate recognition and management. The diagnosis of toxicities associated with immunotherapy in lung cancer can be very challenging and often requires multidisciplinary effort. This mini review gives an overview of the diagnosis and management of immune-related adverse events that arise from using immunotherapy in NSCLC, as well as the potential biomarkers for its early identification and future directions.

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Section: Discussionmentioning

confidence: 99%

Section: Pneumonitismentioning

confidence: 99%

Management of Immune-Related Adverse Events in Patients With Non-Small Cell Lung Cancer

Burke

Rashdan

2021

Front. Oncol.

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“…Autophagy is beneficial to normal cells, but in tumors, it helps malignant cells adjust and adapt to adverse conditions, allowing them to develop and continue to grow. In addition, the PD-1/PD-L1 signaling pathway plays a key role in tumor function and survival (55,56). Autophagy is influenced by the PD-L1 ligand.…”

Section: Autophagymentioning

confidence: 99%

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

Zhu

2021

Front. Immunol.

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Cancer immunotherapy is a kind of therapy that can control and eliminate tumors by restarting and maintaining the tumor-immune cycle and restoring the body’s normal anti-tumor immune response. Although immunotherapy has great potential, it is currently only applicable to patients with certain types of tumors, such as melanoma, lung cancer, and cancer with high mutation load and microsatellite instability, and even in these types of tumors, immunotherapy is not effective for all patients. In order to enhance the effectiveness of tumor immunotherapy, this article reviews the research progress of tumor microenvironment immunotherapy, and studies the mechanism of stimulating and mobilizing immune system to enhance anti-tumor immunity. In this review, we focused on immunotherapy against tumor microenvironment (TME) and discussed the important research progress. TME is the environment for the survival and development of tumor cells, which is composed of cell components and non-cell components; immunotherapy for TME by stimulating or mobilizing the immune system of the body, enhancing the anti-tumor immunity. The checkpoint inhibitors can effectively block the inhibitory immunoregulation, indirectly strengthen the anti-tumor immune response and improve the effect of immunotherapy. We also found the checkpoint inhibitors have brought great changes to the treatment model of advanced tumors, but the clinical treatment results show great individual differences. Based on the close attention to the future development trend of immunotherapy, this study summarized the latest progress of immunotherapy and pointed out a new direction. To study the mechanism of stimulating and mobilizing the immune system to enhance anti-tumor immunity can provide new opportunities for cancer treatment, expand the clinical application scope and effective population of cancer immunotherapy, and improve the survival rate of cancer patients.

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“…A higher TMB means that the cancerous cells generate more new antigens that will be easily recognized by immune cells ( Steuer and Ramalingam, 2018 ). Patients with high TMB values have been found to be sensitive to treatment with immune checkpoint inhibitors (ICIs) in the context of lung cancer, melanoma and urothelial carcinoma ( Chan et al, 2015 ; Powles et al, 2018 ; Reck et al, 2021 ). The advent of ICIs was a milestone event for treatment of advanced tumor and immunotherapy had no advantage over conventional therapy if excluding ICIs ( Zhu et al, 2017 ; Petrelli et al, 2021a ).…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Gene Mutation-Associated Nomogram for Hepatocellular Carcinoma Patients From Four Countries

et al. 2021

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Background: Genomic alteration is the basis of occurrence and development of carcinoma. Specific gene mutation may be associated with the prognosis of hepatocellular carcinoma (HCC) patients without distant or lymphatic metastases. Hence, we developed a nomogram based on prognostic gene mutations that could predict the overall survival of HCC patients at early stage and provide reference for immunotherapy.Methods: HCC cohorts were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The total patient was randomly assigned to training and validation sets. Univariate and multivariate cox analysis were used to select significant variables for construction of nomogram. The support vector machine (SVM) and principal component analysis (PCA) were used to assess the distinguished effect of significant genes. Besides, the nomogram model was evaluated by concordance index, time-dependent receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA). Gene Set Enrichment Analysis (GSEA), CIBERSORT, Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenoscore (IPS) were utilized to explore the potential mechanism of immune-related process and immunotherapy.Results: A total of 695 HCC patients were selected in the process including 495 training patients and 200 validation patients. Nomogram was constructed based on T stage, age, country, mutation status of DOCK2, EYS, MACF1 and TP53. The assessment showed the nomogram has good discrimination and high consistence between predicted and actual data. Furthermore, we found T cell exclusion was the potential mechanism of malignant progression in high-risk group. Meanwhile, low-risk group might be sensitive to immunotherapy and benefit from CTLA-4 blocker treatment.Conclusion: Our research established a nomogram based on mutant genes and clinical parameters, and revealed the underlying association between these risk factors and immune-related process.

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First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1

Cited by 33 publications

References 37 publications

Management of Immune-Related Adverse Events in Patients With Non-Small Cell Lung Cancer

Management of Immune-Related Adverse Events in Patients With Non-Small Cell Lung Cancer

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

Development and Validation of a Gene Mutation-Associated Nomogram for Hepatocellular Carcinoma Patients From Four Countries

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