Dataset Information

Second-Line Treatment of NSCLC-The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms.

ABSTRACT: In contrast to the established role of epidermal growth factor receptor (EGFR) inhibitors for the first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR blockade and of EGFR molecular testing in the second-line treatment remains less clear. The irreversible pan-ErbB family inhibitor afatinib (Gi(l)otrif®) was recently FDA- and EMA-approved for the second-line treatment of NSCLC with squamous cell histology irrespective of the EGFR mutational status (LUX-Lung 8). Contrariwise, results from the TAILOR and DELTA trials among retrospective biomarker analyses show the predictive value of the EGFR mutational status for efficacy of reversible EGFR inhibitors also as a second-line therapy. This mini review critically summarizes the current role of EGFR-targeting strategies in the second-line treatment of NSCLC with special respect to afatinib in light of emerging T790M-specific EGFR and immune check point inhibitors. The review also emphasizes the urgent need for reliable biomarkers to guide therapeutic decision-making and outlines prospective changes to the second-line landscape with some of the current second-line treatment concepts likely to be moved to the first-line.

SUBMITTER: Kohler J

PROVIDER: S-EPMC5303897 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Second-Line Treatment of NSCLC-The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms.

Köhler Jens J

Frontiers in medicine 20170213

In contrast to the established role of epidermal growth factor receptor (EGFR) inhibitors for the first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR blockade and of EGFR molecular testing in the second-line treatment remains less clear. The irreversible pan-ErbB family inhibitor afatinib (Gi(l)otrif®) was recently FDA- and EMA-approved for the second-line treatment of NSCLC with squamous cell his ...[more]

PMID: 28243590

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Project description:Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors. The survival for patients with glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%, this figure has stagnated over the past few decades and survivors still contend with significant long-term debilitating side effects. The prognosis for pineoblastoma is age-dependent, with little chance of a cure for children younger than three years. More effective molecularly targeted strategies are urgently required to treat these cancers. Hyper-activation of epidermal growth factor receptor (EGFR) signaling is characteristic of several different classes of human cancers, including a subset of glioblastoma and medulloblastoma. This has provided the impetus for the development of a suite of EGFR pathway blockers, including second generation irreversible inhibitors, such as dacomitinib. We have developed a comprehensive drug evaluation pipeline, including in vitro interaction analyses and orthotopic xenograft mouse models, to address the efficacy of drugs for brain tumor treatment, enabling the exclusion of potentially ineffective treatments and prioritization of truly beneficial novel treatments for clinical trial. We used this system to examine the effects of dacomitinib as a single agent, or in combination with conventional chemotherapeutics, on the growth of human adult and pediatric brain tumor cell lines. Dacomitinib inhibited EGFR or EGFRvIII activity in vitro in all three tumor types tested, and as a single agent induced a modest increase in survival time for mice bearing glioblastoma, which accurately predicted human clinical trial data. For pediatric medulloblastoma, dacomitinib blocked EGFR/HER signalling in orthotopic xenografts and extended median survival as a single agent, however was antagonistic when used in combination with standard frontline medulloblastoma chemotherapies. The findings caution against the use of dacomitinib for pediatric brain tumor clinical trials.

Dataset Information

Second-Line Treatment of NSCLC-The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms.

Publications

Second-Line Treatment of NSCLC-The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms.

Similar Datasets

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