EML4-ALK rearrangement of lung large cell neuroendocrine carcinoma: a case report

Lung large cell neuroendocrine carcinoma (L-LCNEC) is a subtype of lung cancer with a low incidence and a high degree of malignancy. For early stage patients, surgical treatment is limited, and the risk of postoperative recurrence is high. For patients with unresectable or advanced disease, platinum-based chemotherapy is currently the mainstay of treatment, but its efficacy is unsatisfactory. L-LCNEC with the anaplastic lymphoma kinase (ALK) gene mutation is very rare and currently has no standard therapy. In this article, we report the case of a locally advanced L-LCNEC patient with ALK mutations who underwent first-line treatment with alectinib.

A previously healthy, 46-year-old, non-smoking woman was clinically diagnosed with unresectable locally advanced L-LCNEC. Next generation sequencing (NGS) of the patient's plasma and tumor specimen showed echinoderm microtubule-associated protein-like 4 (EML-4) (exon 13)-ALK (exon 20) fusion with a mutation frequency of 14.48% and 15.37%. The patient refused chemotherapy, and received first-line treatment with alectinib 600 mg, bis in die (bid), per day. After taking alectinib for 1 month, the patient's chest enhanced computed tomography (CT) scan showed a partial response (PR). After 12 months of treatment with alectinib, a radiological evaluation showed that the patient had maintained the PR. A grade 2-3 rash was observed at the beginning of the treatment. After symptomatic treatment, the rash disappeared, and the side effects were fully tolerated. At present, the patient can work normally, has a performance status of 0 and has not experience any major adverse events.

Our case suggests that the first-line use of targeted therapy is also a good choice for L-LCNEC patients of stage III with gene mutations. The side effects are light, the patient can tolerate well, and the quality of life of can be improved.