Oral Sessions

Bohnenberger, Hanibal; Yepes, Diego; Pan, Kuan‐Ting; Emmert, Alexander; Henric-Petri, H.; Bremmer, Felix; Strecker, Jonathan; Lois, Anna-Maria; Fischer, Lauren H.; Küffer, Stefan; Hinterthaner, Marc; Wolff, Hans; Canis, Michel; Sebastian, Martin; Danner, B; Strobel, Pablo; Urlaub, Henning; Oellerich, Thomas

doi:10.1016/s1556-0864(16)30010-7

Cited by 4 publications

(1 citation statement)

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“…EGFR C797S was also detected in tumor re-biopsy samples from a patient who developed acquired resistance to osimertinib [35]. Several other acquired resistance mechanisms were reported in patients who experienced disease progression on osimertinib therapy: acquired EGFR L718Q , small cell transformation, MET amplification, HER2 amplification, BRAF V600E mutation, PIK3CA E545K mutation, loss of EGFR T790M plus alternative pathway activation, and EGFR ligand-dependent activation [36–41]. In a case report, a patient who developed MET amplification responded to therapy with crizotinib, an ALK and MET inhibitor [36].…”

Section: Main Text Of the Reviewmentioning

confidence: 99%

Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors

et al. 2016

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The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (1/2G EGFR-TKIs) gefitinib, erlotinib, and afatinib have all been approved as standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer. The third-generation (3G) EGFR-TKIs have been developed to overcome the EGFR T790M mutation, which is the most common mechanism of acquired resistance to 1/2G EGFR-TKI treatment. This resistance mutation develops in half of the patients who respond to 1/2G EGFR-TKI therapy. The structures of the novel 3G EGFR-TKIs are different from those of 1/2G EGFR-TKIs. Particularly, 3G EGFR-TKIs have lower affinity to wild-type EGFR, and are therefore associated with lower rates of skin and gastrointestinal toxicities. However, many of the adverse events (AEs) that are observed in patients receiving 3G EGFR-TKIs have not been observed in patients receiving 1/2G EGFR-TKIs. Although preclinical studies have revealed many possible mechanisms for these AEs, the causes of some AEs remain unknown. Many mechanisms of resistance to 3G EGFR-TKI therapy have also been reported. Here, we have reviewed the recent clinical and preclinical developments related to novel 3G EGFR-TKIs, including osimertinib, rociletinib, olmutinib, EGF816, and ASP8273.

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Section: Main Text Of the Reviewmentioning

confidence: 99%

Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors

et al. 2016

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Expected Paradigm Shift in Brain Metastases Therapy—Immune Checkpoint Inhibitors

Jindal

Gupta

2018

Mol Neurobiol

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Brain metastasis (BM) is one of the dreadful complications of malignancies. The prognosis after BM is extremely poor and life expectancy is meager. Currently, our treatment modalities are limited to radiotherapy and surgical resection, which also has poor outcomes and leads to various neurological deficits and affects the quality of life of patients. New treatment modality, i.e., immune checkpoint inhibitors, has brought revolution in management of melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors basically enhance the immune response of the body to fight against cancers. Immune response in the brain is highly regulated; therefore, it is challenging to use immune-modulator drugs in BM. The microenvironment of BM is rich in cytotoxic T lymphocytes and which is the target of immune checkpoint inhibitors. Few studies have shown some hope regarding use of immune checkpoint inhibitors in management of BM. It works through inhibiting immune check point gates, i.e., CTLA-4 (cytotoxic T-lymphocyte-associated protein) and PD-1/PD-L1 (programmed cell death protein-1/program death ligand-1). This article explains the basic mechanism of immune check point inhibitors, rationale behind their usage in BM, and some of the clinical studies which have shown the efficacy of immune check point inhibitors in BM.

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Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment

Berghoff

Venur

Preusser

et al. 2016

American Society of Clinical Oncology Educational Book

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Cancer immunotherapy has been a subject of intense research over the last several years, leading to new approaches for modulation of the immune system to treat malignancies. Immune checkpoint inhibitors (anti–CLTA-4 antibodies and anti–PD-1/PD-L1 antibodies) potentiate the host’s own antitumor immune response. These immune checkpoint inhibitors have shown impressive clinical efficacy in advanced melanoma, metastatic kidney cancer, and metastatic non–small cell lung cancer (NSCLC)—all malignancies that frequently cause brain metastases. The immune response in the brain is highly regulated, challenging the treatment of brain metastases with immune-modulatory therapies. The immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes in certain patients and, therefore, may serve as a potential treatment target. However, clinical data of the efficacy of immune checkpoint inhibitors in brain metastases compared with extracranial metastases are limited, as most clinical trials with these new agents excluded patients with active brain metastases. In this article, we review the current scientific evidence of brain metastases biology with specific emphasis on inflammatory tumor microenvironment and the evolving state of clinical application of immune checkpoint inhibitors for patients with brain metastases.

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Oral Sessions

Cited by 4 publications

References 0 publications

Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors

Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors

Expected Paradigm Shift in Brain Metastases Therapy—Immune Checkpoint Inhibitors

Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment

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