Management of brain metastasized non-small cell lung cancer (NSCLC) – From local treatment to new systemic therapies

Tsakonas, Georgios; Petris, Luigi De; Ekman, Simon

doi:10.1016/j.ctrv.2017.02.004

Cited by 47 publications

(40 citation statements)

References 118 publications

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“…The rate of brain metastasis in end-stage non-small cell lung cancer (NSCLC) is up to 44%, especially in adenocarcinoma. 3 Occurrence of brain metastasis is associated with extremely poor prognosis, with a median survival time (MST) of only 1-2 months in untreated patients. 4 Among patients receiving standardized radiotherapy, the MST is only 8.8 months.…”

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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“…The prognosis of such patients is generally poor, with a median survival ranging from 2 to 6 months in the past [33]. Treatment options for these patients before the era of targeted therapy were quite limited, including only WBRT, stereotactic radiosurgery, surgery and chemotherapy [34]. Although these therapeutic methods could be combined with each other, the efficacy results is not as good as enough.…”

Section: Discussionmentioning

confidence: 99%

Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer

et al. 2020

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“…Importantly, traditional chemotherapeutical methods could lead to multiple side effects including nausea, emesis, anorexia and myelosuppression. What is more, neurocognitive dysfunction and declines in quality of life is unavoidable for certain patients receiving WBRT treatment, which occurred in several months to years after initial cerebral radiotherapy [32][33][34] . Thus, novel treatment strategy with relatively tolerable toxicity is urgently needed.…”

Section: Discussionmentioning

confidence: 99%

Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer

Jiang

Zhang

et al. 2019

Preprint

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Background: The prognosis of non-small-cell lung cancer (NSCLC) with brain metastases is very poor. Currently, therapeutic methods for this patient population include whole-brain radiation therapy (WBRT), surgery, radiosurgery and systemic treatment. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could be effective on cerebral metastases of mutated NSCLC. However, which EGFR-TKIs is more appropriate is still unknown. Methods: A total of 43 patients were recruit in this study. Patients received either icotinib (125 mg, thrice a day) or geﬁtinib (250 mg, once a day) until disease progression or unacceptable toxicity. The primary end point of this study was PFS. The relationships between therapeutic arms and patients characteristics were performed using Pearson’s chi-square test or Fisher’s exact test. The differences in PFS among the two arms were analyzed using Kaplan-Meier curves and log rank tests. Results: There was no significant difference of intracranial ORR (66.6% versus 59.1%, P =0.62) and DCR (85.7% versus 81.8%, P =0.73) between the two arms. The median intracranial PFS (iPFS) for icotinib and gefitinib arms were 8.4 months (95% CI, 5.4 to 11.3 months) and 10.6 months (95% CI, 6.3 to 14.8 months), respectively (P =0.17). Adverse events of the two study arms were generally mild. None of the patients experienced dose reduction of EGFR-TKIs. Conclusions: Our study showed that icotinib and geﬁtinib had similar efficacy for brain metastasis of EGFR mutated NSCLC. Large randomized studies are suggested to further illuminate the effect of these two EGFR-TKIs on cerebral lesions of NSCLC.

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Management of brain metastasized non-small cell lung cancer (NSCLC) – From local treatment to new systemic therapies

Cited by 47 publications

References 118 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>

Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer

Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer

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