Synergies of Targeting Tumor Angiogenesis and Immune Checkpoints in Non-Small Cell Lung Cancer and Renal Cell Cancer: From Basic Concepts to Clinical Reality

Purpose We aimed to elucidate predictive factors for the development of immune-related adverse events (iraes) in patients receiving immunotherapies for the management of advanced solid cancers.Methods This retrospective study involved all patients with histologically confirmed metastatic or inoperable melanoma, non-small-cell lung cancer, or renal cell carcinoma receiving immunotherapy at the Cancer Centre of Southeastern Ontario. The type and severity of iraes, as well as potential protective and exacerbating factors, were collected from patient charts.ResultsThe study included 78 patients receiving ipilimumab (32%), nivolumab (33%), or pembrolizumab (35%). Melanoma, non-small-cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the cancers in the study population. In 41 patients (53%) iraes developed, with multiple iraes developing in 12 patients (15%). In most patients (70%), the iraes were of severity grade 1 or 2. Female sex [adjusted odds ratio (oradj): 0.094; 95% confidence interval (ci): 0.021 to 0.415; p = 0.002] and corticosteroid use before immunotherapy (oradj: 0.143; 95% ci: 0.036 to 0.562; p = 0.005) were found to be associated with a protective effect against iraes. In contrast, a history of autoimmune disease (oradj: 9.55; 95% ci: 1.34 to 68.22; p = 0.025), use of ctla-4 inhibitors (oradj: 6.25; 95% ci: 1.61 to 24.25; p = 0.008), and poor kidney function of grade 3 or greater (oradj: 10.66; 95% ci: 2.41 to 47.12; p = 0.025) were associated with a higher risk of developing iraes. A Hosmer–Lemeshow goodness-of-fit test demonstrated that the logistic regression model was effective at predicting the development of iraes (chi-square: 1.596; df = 7; p = 0.979).Conclusions Our study highlights several factors that affect the development of iraes in patients receiving immunotherapy. Although future studies are needed to validate the resulting model, findings from the study can help to guide risk stratification, monitoring, and management of iraes in patients given immunotherapy for advanced cancer.

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Immunotherapy for Advanced Small Cell Lung Cancer: A Case Report

Journal of Clinical Case Studies ◽

10.16966/2471-4925.235 ◽

2021 ◽

Vol 6 (5) ◽

Author(s):

Wang J ◽

Deng C ◽

Zhu X ◽

Zou X ◽

Wang J

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Malignant Tumors ◽

Small Cell ◽

Immune Checkpoints ◽

Small Cell Lung ◽

Advanced Stages ◽

Made In

In recent years, extraordinary achievements have been made in treating tumor immune checkpoints as targets, which significantly contributes to the research and development of novel immunologic drugs and their application in treating malignant tumors. However, few immunologic drugs can be administered to treat Small Cell Lung Cancer (SCLC). Currently, the focus of most clinical studies is placed on treating SCLC with a combination of immunotherapy and chemotherapy, which is relatively expensive and not covered by medical insurance, thus imposing a heavy economic burden on patients. Meanwhile, obvious adverse reactions occur during chemotherapy, which is still unacceptable to many patients and hence has not yet been widely adopted in clinical practice. Therefore, whether immunotherapy alone can help patients with SCLC, improve their quality of life, and prolong their survival time is a topic we will study in the future. In this case, an attempt was made to apply camrelizumab, an immunologic drug, in the treatment of SCLC in advanced stages, and a favorable efficacy was achieved.

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Combination of Cytokine-Induced Killer Cells and Programmed Cell Death-1 Blockade Works Synergistically to Enhance Therapeutic Efficacy in Metastatic Renal Cell Carcinoma and Non-Small Cell Lung Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2018.01513 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 4

Author(s):

Zibing Wang ◽

Xiaoli Liu ◽

Brian Till ◽

Miaomiao Sun ◽

Xiang Li ◽

...

Keyword(s):

Lung Cancer ◽

Renal Cell Carcinoma ◽

Cell Death ◽

Programmed Cell Death ◽

Small Cell Lung Cancer ◽

Renal Cell ◽

Therapeutic Efficacy ◽

Small Cell ◽

Small Cell Lung ◽

Programmed Cell Death 1

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Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.3.806 ◽

1996 ◽

Vol 14 (3) ◽

pp. 806-813 ◽

Cited By ~ 75

Author(s):

B E Johnson ◽

J D Bridges ◽

M Sobczeck ◽

J Gray ◽

R I Linnoila ◽

...

Keyword(s):

Lung Cancer ◽

Survival Rate ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cell Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Cns Metastases ◽

Small Cell Cancer ◽

Limited Stage

PURPOSE A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival. PATIENTS AND METHODS Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen. RESULTS Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have had progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival time is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years. CONCLUSION This combined modality regimen for patients with limited-stage small-cell lung cancer results in a 2-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths.

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