Capmatinib for patients with non-small cell lung cancer with MET exon 14 skipping mutations: A review of preclinical and clinical studies

Small cell lung cancer (SCLC) represents approximately 15% of all lung cancers, and is the most aggressive form of lung cancer. Left untreated, the time from diagnosis to death is 2–3 months. With current treatment, expected survival is 7–20 months, depending on the stage of disease. A new drug, amrubicin, is approved in Japan for lung cancer and has demonstrated efficacy in U.S. and European phase II trials of SCLC patients with either untreated disease or relapsed refractory illness. In a phase II study of amrubicin in previously untreated patients, response rates reached 75% with a median survival time of almost 1 year. Amrubicin is a fully synthetic 9-aminoanthracycline, and an analog of doxorubicin and epirubicin. The major mechanism of action of amrubicin is inhibition of topoisomerase II. Unlike doxorubicin, however, it exhibits little or no cardiotoxicity in clinical studies and preclinical models. In preclinical rodent tumor models, it is selectively distributed to tumour tissue and is not detected in the heart when compared with doxorubicin, which is distributed equivalently to these sites. The primary metabolite of amrubicin, amrubicinol, is up to 100 times more cytotoxic in vitro than the parent compound. This review describes the mechanisms of action of amrubicin as well as clinical studies which demonstrate the potential of this drug in future SCLC treatment. The review also puts forward hypothetical considerations for the use of other drugs such as lenalidomide, an immunomodulatory drug acting on multiple signalling pathways, or histone deacetylase inhibitors, in combination with amrubicin in SCLC.

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First-line afatinib for the treatment of EGFR mutation-positive non-small-cell lung cancer in the ‘real-world’ clinical setting

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919836374 ◽

2019 ◽

Vol 11 ◽

pp. 175883591983637 ◽

Cited By ~ 5

Author(s):

Keunchil Park ◽

Darren Wan-Teck Lim ◽

Isamu Okamoto ◽

James Chih-Hsin Yang

Keyword(s):

Lung Cancer ◽

Clinical Practice ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Real World ◽

Clinical Studies ◽

Egfr Mutation ◽

Small Cell ◽

Small Cell Lung ◽

First Line

Afatinib is an ErbB family blocker that is approved for the treatment of epidermal growth factor receptor ( EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Pivotal randomized clinical studies demonstrated that afatinib significantly prolonged progression-free survival compared with platinum-based chemotherapy (LUX-Lung 3, LUX-Lung 6), and with gefitinib (LUX-Lung 7), with manageable side effects. However, these results were derived from controlled studies conducted in selected patients and are not necessarily representative of real-world use of afatinib. To gain a broader understanding of the effectiveness and safety of first-line afatinib, we have undertaken a literature review of real-world studies that have assessed its use in a variety of patient populations. We focused on patients with uncommon EGFR mutations, brain metastases, or those of advanced age, as these patients are often excluded from clinical studies but are regularly seen in routine clinical practice. The available real-world studies suggest that afatinib has clinical activity, and is tolerable, in diverse patient populations in an everyday clinical practice setting. Moreover, consistent with LUX-Lung 7, several real-world comparative studies indicate that afatinib might confer better efficacy than first-generation EGFR tyrosine kinase inhibitors. Tolerability-guided dose adjustment, undertaken in 21–68% of patients in clinical practice, did not appear to reduce the efficacy of afatinib. Taken together, these findings provide further support for the use of afatinib as a treatment option in patients with EGFR mutation-positive NSCLC.

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