Efficacy of immune checkpoint inhibitors in patients with brain metastasis from NSCLC, RCC, and melanoma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 214-214 ◽  
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Xuefei Jia ◽  
Manmeet Singh Ahluwalia
Keyword(s):  
Brain Metastasis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Tertiary Care ◽  
Multivariable Analysis ◽  
Volumetric Analysis ◽  
Cell Lung Carcinoma ◽  
Combination Methods

214 Background: Immune checkpoint inhibitors are revolutionizing the treatment of multiple advanced malignancies, however, there is limited data on the efficacy of immune checkpoint blockade in brain metastasis. We conducted a study to analyze the overall survival (OS) and progression-free survival (PFS) among patients with brain metastasis from Non-Small Cell Lung Carcinoma (NSCLC), Renal Cell Carcinoma (RCC), and Melanoma treated with either Nivolumab, Pembrolizumab, Ipilimumab or a combination. Methods: After IRB approval, we retrospectively evaluated patients with brain metastasis treated at our tertiary care institution from 2011-2017 who underwent immunotherapy and one or more of the following; whole brain radiation therapy (WBRT), surgery, stereotactic radiosurgery (SRS) or systemic chemotherapy. Univariable and multivariable analysis was utilized to analyze OS and PFS. Volumetric analysis to assess treatment response is ongoing. Results: A total of 128 patients were identified with a median age of 60.6 years. 49% of patients were male; 77% of patients had a good (0 or 1) ECOG performance scores at the time of the brain metastasis; 83 patients had supratentorial brain metastasis, 11 had infratentorial and 24 had both. The prevalence of mutations was 34% in NSCLC patients, 58% in melanoma, and 0% in RCC. The median OS from the start of immunotherapy was not reached for RCC and was 17.1 and 28.9 months for Melanoma and NSCLC respectively. Median PFS was 5.9, 6.7 and 3.6 months for RCC, Melanoma, and NSCLC respectively. On multivariable analysis, SRS, sex and the number of cycles of immunotherapy had statistically significant hazard ratios. Conclusions: Immune checkpoint inhibitors are efficacious in the treatment of brain metastasis. Further analysis including response criteria using volumetric analysis is ongoing and final results will be presented at the meeting. [Table: see text]

scholarly journals Immunotherapy in head and neck cancer

2019 ◽  
Vol 65 (2) ◽  
Author(s):  
Mateusz Sikora ◽  
Rafał Becht
Keyword(s):  
Immune System ◽  
Head And Neck ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Malignant Neoplasms ◽  
Cell Lung Carcinoma ◽  
Positive Effects

Immunotherapy is a method for the systemic treatment of malignant neoplasms. It is based on the abolition of the immunosuppressive effect of cancer cells and is meant to mobilize the host’s immune system to actively combat with the disease. The group of cancers which are closely connected with the immune system includes: melanoma, non-small cell lung carcinoma (NSCLC), renal cancer, colon cancer, Hodgkin’s lymphoma, and head and neck squamous cell carcinoma (HNSCC). Currently, cancer immunotherapy involves treatment with immune checkpoint inhibitors, therapeutic cancer vaccines, oncolytic virotherapy, and monoclonal antibodies. In the case of HNSCC, the most frequently used method is treatment with immune checkpoint inhibitors. An example of an immunological checkpoint is programmed cell death protein-1 (PD-1), which may be activated in the process of carcinogenesis to repeal immune surveillance, favouring the development of neoplasm. The function of immune checkpoint inhibitors is based on abolition of the immunosuppressive influence of cancerous cells. Clinical trials show the positive effects of treating HNSCC with immunotherapy in certain patients. In comparison to standard systemic treatment with chemotherapy, immunotherapy rarely causes treatment-related adverse events (TRAEs). Greater survival and treatment response are factors which encourage the further development of immuno-oncology. In this article, we present a review of literature concerning the use of immunotherapy in the treatment of HNSCC.

scholarly journals Challenges of Immunotherapy in Stage IV Non–Small-Cell Lung Cancer

2021 ◽  
pp. OP.20.00949
Author(s):  
Sophie Stock-Martineau ◽  
Kate Magner ◽  
Kevin Jao ◽  
Paul Wheatley-Price
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Programmed Death

Treatment for metastatic non–small-cell lung carcinoma has seen important advances in recent years with the introduction of targeted therapies and immunotherapy. Immune checkpoint inhibitors, which target the programmed death 1 receptor and programmed death ligand-1, alone or in combination with platinum-based chemotherapy, have become standard of care in the first-line setting for patients with advanced non–small-cell lung carcinoma without targetable driver mutations. However, several clinical questions have now since emerged. Physicians treating lung cancer lack guidance when treating patients who have a poor performance status, patients who are receiving corticosteroids, and those known for pre-existing autoimmune disorders. Furthermore, data are scarce on rechallenging a patient with immune checkpoint inhibitors after the occurrence of a significant immune-related adverse event. In this review, we aim to shed light on these topics.

Immune checkpoint inhibitors in the treatment of cancer

2021 ◽  
Vol 16 ◽  
Author(s):  
Wissam Zam ◽  
Lina Ali
Keyword(s):  
T Cell Activation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Research Field ◽  
Cell Lung Carcinoma ◽  
Checkpoint Proteins

Background: Immunotherapy drugs, known as immune checkpoint inhibitors (ICIs), work by blocking checkpoint proteins from binding with their partner proteins. The two main pathways that are specifically targeted in clinical practice are cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) that showed potent immune-modulatory effects through their function as negative regulators of T cell activation. Methods: In view of the rapid and extensive development of this research field, we conducted a comprehensive review of the literature and update on the use of CTLA-4, PD-1 and PD-L1 targeted therapy in the treatment of several types of cancer including melanoma, non-small-cell lung carcinoma, breast cancer, hepatocellular carcinoma, hodgkin lymphoma, cervical cancer, head and neck squamous cell carcinoma. Results: Based on the last updated list released on March 2019, seven ICIs are approved by the FDA including ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, and cemiplimab. Conclusion: This review also highlighted the most common adverse effects caused by ICIs and which affect people in different ways.

scholarly journals Immune checkpoint inhibitors for the management of advanced non–small-cell lung carcinoma

2020 ◽  
Vol 31 (6) ◽  
pp. 637-645 ◽  
Author(s):  
Li-ting Lai ◽  
Zheng-yu Zhan ◽  
Miao Feng ◽  
Fan Li ◽  
Lin-feng Lai ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

scholarly journals Lazarus-type tumour response to therapy with nivolumab for sarcomatoid carcinomas of the lung

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
C. Roesel ◽  
K. Kambartel ◽  
U. Kopeika ◽  
A. Berzins ◽  
T. Voshaar ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Lung Resection ◽  
Sarcomatoid Carcinoma ◽  
Tumour Response ◽  
Response To Therapy ◽  
Cell Lung Carcinoma ◽  
Response To Chemotherapy

Pulmonary sarcomatoid carcinoma (psc) is a rare subtype of non-small-cell lung carcinoma with a poor prognosis and poor response to chemotherapy and radiotherapy. A previous study reported that psc expresses high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumours. We report 2 cases of patients with a lung sarcomatoid carcinoma. Both patients initially underwent curative lung resection, but developed early recurrent disease. Because PD-L1 was highly expressed in the tumour cells, we initiated therapy with nivolumab, which showed good efficacy, almost complete radiologic tumour remission, and a remarkable improvement in the condition of those patients. Immune checkpoint inhibitors targeting PD-1 might be a valuable therapy option for pscs.

scholarly journals THER-16. EFFICACY OF UPFRONT IMMUNE CHECKPOINT INHIBITORS IN LUNG CANCER BRAIN METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i14-i14
Author(s):  
Addison Barnett ◽  
Adam Lauko ◽  
Assad Ali ◽  
Hong Li ◽  
Soumya Sagar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Proportional Hazards Model ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
Primary Lung Cancer ◽  
Cox Proportional Hazards Model ◽  
Rank Test

Abstract INTRODUCTION: Immune checkpoint inhibitors (ICI) have resulted in improved outcomes in a subset of patients with lung cancer. However, data describing the efficacy of ICI in lung cancer brain metastasis (LCBM) is limited. We analyzed overall survival (OS) in patients with LCBM treated with upfront ICI, defined as having received ICI within 90 days of LCBM diagnosis, compared to non-ICI therapies. METHODS: We reviewed 665 patients with LCBM who were diagnosed between 2000 and 2018 at a major tertiary care institution. Of those patients, 240 received ICI, 164 of which received ICI after 90 days and 76 received ICI within 90 days. Propensity score (PS) was calculated using a logistic regression model including age, KPS, number of baseline brain lesions, and presence of extra-cranial metastasis (ECM) at the time of BM diagnosis. OS from BM diagnosis between PS matched cohorts were compared using Kaplan-Meier, the Log-Rank test, and Cox proportional hazards model. RESULTS: Prior to PS matching, median survival between ICI and non-ICI cohorts was not significantly different (10.9 months for both, p=0.81), although more ICI patients had ECM (57.1% vs 40.9%, p=0.006). Following PS matching, the ICI (n=76) and non-ICI (n=76) cohorts had a median age (62.4 vs 62.3 years), KPS (80 for both), lesion number (2 for both), and ECM (56.6% for both). Of matched patients, 94% received SRS, 52% received WBRT, and 29% underwent surgical resection. Compared to non-ICI, the ICI cohort has a 2-year OS hazard ratio, HR=0.87 (95% CI=0.58–1.31, p=0.51). Median and 1-year survival were not significantly different between ICI and non-ICI cohorts (median: 10.9 vs 9.1 months; 1-yr: 43.0% vs 42.4%). CONCLUSION: Patients with BM from primary lung cancer who received ICI within 90 days of their BM diagnosis did not have improvement in OS compared to patients who received non-ICI therapies.

scholarly journals CMET-12. EFFICACY OF UPFRONT IMMUNE CHECKPOINT INHIBITORS IN LUNG CANCER BRAIN METASTASIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi53-vi53
Author(s):  
Addison Barnett ◽  
Adam Lauko ◽  
Hong Li ◽  
Assad Ali ◽  
Soumya Sagar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Cox Proportional Hazards Models

Abstract INTRO/OBJECTIVE Immune checkpoint inhibitors (ICI) have improved outcomes in a subset of patients with lung cancer. However, data describing the efficacy of ICI in lung cancer brain metastasis (LCBM) is limited. We analyzed overall survival (OS) in patients with LCBM treated with upfront ICI, defined as having received ICI within 90-days of LCBM diagnosis, compared to non-ICI therapies. METHODS We reviewed 665 patients with LCBM diagnosed between 2000 and 2018 at a major tertiary care institution. Of those patients, 240 received ICI, 164 of which received ICI after 90-days and 76 received ICI within 90-days. Propensity score (PS) was calculated by logistic regression model including age, KPS, number of baseline brain lesions, and presence of extra-cranial metastasis (ECM) at time of LCBM diagnosis. OS from LCBM diagnosis between PS matched cohorts were compared using Kaplan-Meier, the Log-Rank test, and Cox proportional hazards models. RESULTS Prior to PS matching, median survival between ICI and non-ICI cohorts was not significantly different (10.9 months for both, p=0.81), although more ICI patients had ECM (57.1% vs 40.9%, p=0.006). Following PS matching, the ICI (n=76) and non-ICI (n=76) cohorts had median age (62.4 vs 62.3 years), KPS (80 for both), lesion number (2 for both), and ECM (56.6% for both). Of matched patients, 94% received SRS, 52% received WBRT, and 29% underwent surgical resection. Compared to non-ICI, the ICI cohort had a 2-year OS hazard ratio=0.87 (95% CI=0.58–1.31, p=0.51). Median and 1-year survival were not significantly different between ICI and non-ICI cohorts (median: 10.9 vs 9.1 months; 1-yr: 43.0% vs 42.4%). CONCLUSION Patients with LCBM who received ICI within 90-days of their diagnosis did not have improvement in OS compared to patients who received non-ICI therapies. Evaluation of clinical factors that may affect the efficacy and durability of immunotherapy is ongoing and will be presented.

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