Trends in ALK inhibitors for non-small cell lung cancer

Background: Rearrangements in the gene encoding anaplastic lymphocyte kinase (ALK) are found in 3%–5% of patients. Treatment options have significantly expanded with ALK inhibitor drug approvals including crizotinib in 2011, ceritinib in 2014, alectinib in 2015, brigatinib in 2017 and lorlatinib in 2018. We sought to better understand the real-world treatment utilization and cost of ALK inhibitors in lung cancer (LCA) over the most recent period for which adjudicated claims are available, October 2017-September 2018... Conclusions: Our analyses demonstrate alectinib is the preferred first-line ALK inhibitor in the last twelve months of available data. Furthermore, the increased ER and in-patient costs may substantiate the findings of the ALEX trial, notably higher liver toxicity and more nausea, vomiting, and diarrhea for crizotinib. There is not yet sufficient data on the newer ALK inhibitors, brigatinib and lorlatinib in the real-world. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.e14046

Authors: Denise Meade, Marie Ng, S Alford

Real-World OutcomesKirk SmithMay 25, 2020ALK, inhibitor, non-small cell lung cancer

Anaplastic lymphoma kinase inhibitor-associated myositis

Anaplastic lymphoma kinase (ALK) inhibitors have been used in patients with non-small cell lung cancer (NSCLC) harboring EML4-ALK fusion gene.1 Severe skeletal muscle adverse events of ALK inhibitors, such as muscle weakness, have seldom been reported.2,3 Herein, we describe a patient who showed a severe skeletal muscle deficit after the administration of the ALK inhibitor, alectinib, and was successfully treated by corticosteroids without withdrawal from the cancer therapy READ ARTICLE

Neurology: Neuroimmunology & Neuroinflammation DOI:10.1212/NXI.0000000000000735

Authors: Akinori Uruha, Stefan Kliesch, Simone Schmid, Carsten Dittmayer, Hans-Hilmar Goebel, Alexander Dressel, Werner Stenzel, Robert Handreka

Case StudyKirk SmithMay 6, 2020Alk, inhibitor, myositis, corticosteroids

Design, synthesis of orally bioavailable novel anaplastic lymphoma kinase (ALK) inhibitor diphenylaminopyrimidine analogs and efficacy study on NCI-H2228 xenografts mice model

Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of non-small cell lung cancer (NSCLC). Within our ALK drug discovery program, we identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound 11 showed better in vitro activity and in vivo efficacy with good pharmacokinetic profile. In vivo efficacy of compound 11 was better than standard drug ceritinib in NCI-H2228 xenograft mice model. READ ARTICLE

Bioorganic & Medicinal Chemistry Letters DOI:10.1016/j.bmcl.2019.04.012

Authors: Debasis Das, Jingbing Wang, Yong Li, Jingli Shi, Jian Hong

Meta-analysis comparing incidence of grade 3–4 neutropenia with ALK inhibitors and chemotherapy in patients with non-small-cell lung cancer

Aim: Using the available literature, this meta-analysis aimed to compare reports of the incidence of grade 3–4 neutropenia with ALK inhibitors and chemotherapy in patients with ALK-positive NSCLC. Conclusion: This meta-analysis of Phase III randomized clinical trials found no significant difference in the incidence of grade 3–4 neutropenia among patients with ALK-positive NSCLC treated with either an ALK inhibitor or chemotherapy, and this was not affected by adjusting for baseline tumor stage. READ ARTICLE

FUTURE ONCOLOGY
DOI:10.2217/fon-2018-0863

Authors: Bernardo Rapoport, Ramin B Arani, Nicola Mathieson, Andriy Krendyukov