Expected Paradigm Shift in Brain Metastases Therapy—Immune Checkpoint Inhibitors

Jindal, Vishal; Gupta, Sorab

doi:10.1007/s12035-018-0905-3

Cited by 21 publications

(20 citation statements)

References 72 publications

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“…7 Localized treatments have become mainstream, but may increase the incidencerate of complex postoperative diseases such as stroke, organ thanatosis, and cognizant confusion. 8 Generalized immunotherapy has shown favorable data in the treatment of brain metastases and has changed the conventionalpattern of cerebral immune privilege. The immune system recognizes tumor cell antigens, and antigen presenting cells (APCs) activate T cells and subsequent T cell toxicity via APCs, and play an important role in clearing tumor clones.…”

Section: Introductionmentioning

confidence: 99%

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Wang

Xie

et al. 2020

OTT

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The central nervous system (CNS) is regarded as an immune privileged environment; however, changes in the neuroimmunology paradigm have led to an increased interest in systematic immunotherapy in lung cancer therapy. The presence of the lymphatic system in the CNS as well as the physiological and biochemical changes in the blood-brain barrier in the tumor microenvironment suggests that immunocytes are fully capable of entering and exiting the CNS. Emerging clinical data suggest that inhibitors of programmed death receptor-1/programmed death ligand 1 (PD-1/PD-L1) can stimulate surrounding T cells and thus have antitumor effects in the CNS. For example, PD-1 antibody (pembrolizumab) monotherapy has displayed a 20-30% encephalic response rate in patients with brain metastases from malignant melanoma or non-small cell lung cancer. Combined application of nivolumab and ipilimumab anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 showed an encephalic response rate of 55% in patients with brain metastases of melanoma. Further evidence is required to verify these response rates and identify the mechanisms of curative effects and drug tolerance. While regional treatments such as whole-brain radiosurgery, stereotactic radiosurgery, and brain surgery remain the mainstream, PD-1/PD-L1 inhibitors display potential decreased neurotoxic effects. To date, five drugs have been approved for use in patients with encephalic metastases of lung carcinoma: the anti-PD-1 drugs, pembrolizumab and nivolumab, and the anti-PD-L1 agents, atezolizumab, durvalumab, and avelumab. In recent years, clinical trials of inhibitors in combination with other drugs to treat brain metastasis have also emerged. This review summarizes the biological principles of PD-1/PD-L1 immunotherapy for brain metastasis of lung cancer, as well as ongoing clinical trials to explore unmet needs.

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Section: Introductionmentioning

confidence: 99%

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Wang

Xie

et al. 2020

OTT

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“…ICIs are a revolution for the management of cancers and have shown benefits for BM management. In the long term, if these drugs prolong survival and improve the quality of life of patients with BM, it will be a new era for BM management …”

Section: Discussionmentioning

confidence: 99%

“…CNS responses were similarly durable for NSCLC, ranging from three to seven months, with five of the six continuing to respond at the time of data analysis. 15,16 Regarding safety, three patients (17%) experienced transient grade 3 cognitive dysfunction and grade 1-2 seizures. Similar clinical trials were conducted with nivolumab.…”

Section: Discussionmentioning

confidence: 99%

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Pembrolizumab for non‐small cell lung cancer with central nervous system metastases: A two‐case report

Zhang

2019

Thoracic Cancer

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Non‐small cell lung cancer (NSCLC) accounts for up to 85% of all lung cancers. Central nervous system metastases are a common complication of NSCLC and confer a poor prognosis and a dismal survival rate. Treatment is limited, has poor outcomes, and affects patient quality of life. Pembrolizumab is an anti‐PD‐1 antibody that has shown good results for the management of NSCLC. However, its penetration of the central nervous system has not been well studied, and patients with untreated brain metastases are excluded from most clinical trials. Herein, we report two cases of NSCLC with brain metastases in patients successfully treated with pembrolizumab, and discuss the efficacy and safety of pembrolizumab in these patients. Pembrolizumab has shown good control and the patients have had long progression‐free survival with a high quality of life. Neither patient has experienced serious or grade 3–4 treatment‐related adverse events. Pembrolizumab demonstrates activity in brain metastases in NSCLC patients with an acceptable safety profile. Thus, there may be a role for systemic immunotherapy in patients with untreated or progressive brain metastases.

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“…However, the neurodegenerative effects of WBRT can cause substantial morbidity and impair quality of life while having only a moderately beneficial effect on overall survival. 55 To minimize neurocognitive damage from WBRT, novel radiation techniques are currently being explored. Hippocampal-sparing WBRT reduces the radiation exposure of the hippocampus while preserving the therapeutic benefit on the grounds that the hippocampus has a low frequency of brain metastasis occurrences, while WBRT-induced hippocampal damage is frequently associated with neurotoxicity.…”

Section: Definitive Treatments For Brain Metastasesmentioning

confidence: 99%

Tyrosine Kinase Inhibitor Therapy for Brain Metastases in Non-Small-Cell Lung Cancer: A Primer for Radiologists

Dodson

Richards

Smith

et al. 2020

AJNR Am J Neuroradiol

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Treatment options for patients who develop brain metastases secondary to non-small-cell lung cancer have rapidly expanded in recent years. As a key adjunct to surgical and radiation therapy options, systemic therapies are now a critical component of the oncologic management of metastatic CNS disease in many patients with non-small-cell lung cancer. The aim of this review article was to provide a guide for radiologists, outlining the role of systemic therapies in metastatic non-small-cell lung cancer, with a focus on tyrosine kinase inhibitors. The critical role of the blood-brain barrier in the development of systemic therapies will be described. The final sections of this review will provide an overview of current imaging-based guidelines for therapy response. The utility of the Response Assessment in Neuro-Oncology criteria will be discussed, with a focus on how to use the response criteria in the assessment of patients treated with systemic and traditional therapies. ABBREVIATIONS: ALK ¼ anaplastic lymphoma kinase; CTLA-4 ¼ cytotoxic T-lymphocyte-associated protein 4; EGFR ¼ epidermal growth factor receptor; EML4 ¼ echinoderm microtubule-associated protein-like 4; ICI ¼ immune checkpoint inhibitor; NSCLC ¼ non-small-cell lung cancer; PD-1 ¼ programmed cell death protein 1; PFS ¼ progression-free survival; PRES ¼ posterior reversible encephalopathy syndrome; QALY ¼ quality-adjusted life years; RANO ¼ Response Assessment in Neuro-Oncology; RECIST ¼ Response Evaluation Criteria in Solid Tumors; ROS1 ¼ C-ras oncogene 1; SRS ¼ stereotactic radiosurgery; TKI ¼ tyrosine kinase inhibitor; WBRT ¼ whole-brain radiation therapyIndicates open access to non-subscribers at www.ajnr.org

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Expected Paradigm Shift in Brain Metastases Therapy—Immune Checkpoint Inhibitors

Cited by 21 publications

References 72 publications

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Pembrolizumab for non‐small cell lung cancer with central nervous system metastases: A two‐case report

Tyrosine Kinase Inhibitor Therapy for Brain Metastases in Non-Small-Cell Lung Cancer: A Primer for Radiologists

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