by Dr. C.H. Weaver M.D. 12/2018
The combination of Iressa (gefitinib) and the experimental medication Capmatinib appears to be safe and effective for the treatment of epidermal growth factor receptor (EGFR)-mutated, mesenchymal-epithelial transition (Met) factor-dysregulated non–small-cell lung cancer (NSCLC).
Lung cancer is the number one cause of cancer-related deaths in the United States. Research identifying specific molecular and genetic components of a patient’s cancer cells has led to the development of precision cancer medicines that target and treat lung cancers based on their individual characteristics.
The EGFR is involved in cellular replication and growth, and a mutation within the EGFR can lead to the development and spread of cancer cells. Patients with NSCLC that has an EGFR mutation are treated with EGFR tyrosine kinase inhibitor drugs that block the effects of the mutated EGFR.
Iressa is one of several EGFR drugs that are used for the treatment of patients whose cancer express’s the most common type of EGFR mutations in NSCLC (exon 19 deletions or exon 21 L858R substitution gene mutations).
Capmatinib is an oral medication that inhibits the proto-oncogene c-Met’s anticancer activity. c-Met is a protein that in humans is encoded by the MET gene. The c-Met protein possesses tyrosine kinase activity and plays a key role in cancer cell proliferation, survival, invasion, metastasis, and angiogenesis. Capmatinib selectively inhibits c-Met phosphorylation and disrupts c-Met signal transduction pathways leading to cell death in cancer cells overexpressing the c-Met protein.
Researchers believe that combining EGFR and c-Met inhibition may lead to improved anti-cancer responses in NSCLC. To thest this approach doctors performed a phase 1b/2 clinical trial in 161 patients with EGFR-mutated, MET-dysregulated NSCLC that had progressed during prior EGFR-tyrosine kinase inhibitor treatment. Patients were treated with the combination of Iressa, and capmatinib capsules at varying doses. The combination therapy was generally well tolerated and overall 47% of individuals responded to treatment and 73% were reported to have either responsive or stable disease.
The study results, published in the Journal of Clinical Oncology demonstrate that the combination of capmatinib and Iressa is feasible, rational and may be a promising treatment option for patients with EGFR-mutated, MET-dysregulated NSCLC. The continued development of capmatinib is occurring in clinical trials.
- Wu YL, Zhang L, Kim DW, et al. Phase Ib/II study of capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated, MET factor–dysregulated non–small-cell lung cancer. J Clin Oncol. 2018;36:3101-3109. doi: 10.1200/JCO.2018.77.7326