Combinatorial therapy is a safe and durable treatment option in -rearranged non-small cell lung cancer with an acquired exon 14 skipping mutation mediated resistance to alectinib: a case report.

BACKGROUND

Anaplastic lymphoma kinase () tyrosine kinase inhibitors (TKIs) are standard first line treatment for rearranged non-small cell lung cancer (NSCLC) and have demonstrated high and durable response rates. Despite these initial responses, patients eventually develop resistance through dependent and independent alterations. These resistance mechanisms have made treatment decisions increasingly more complex. Here we describe a case of an acquired mesenchymal epithelial transition factor () exon 14 skipping () mutation mediated resistance to alectinib in a patient with -rearranged lung adenocarcinoma.

CASE DESCRIPTION

We present a 72-year-old male with a 2-pack year smoking history and end-stage renal disease on hemodialysis diagnosed with metastatic lung adenocarcinoma harboring an echinoderm microtubule-associated protein 4 () fusion gene mutation. The patient was initially treated with alectinib with good response. However, the patient eventually developed resistance. Next generation sequencing of a liquid biopsy at time of progression revealed a exon 14 skip mutation. The patient was started on dual alectinib and capmatinib therapy, which led to a rapid and durable response.

CONCLUSIONS

This is the first case report of the successful treatment of mutation mediated resistance to alectinib with combination therapy of alectinib and capmatinib, which led to a rapid and durable response in our patient. This case highlights the importance of resequencing patients at the time of progression to identify potential actionable dependent and independent resistance alterations. Combinatorial therapy may provide a promising effective and safe therapy option for patients who acquire resistance after initial TKI therapy.