Short-term response to alectinib and rapid progression in a lung squamous cell carcinoma patient harboring an...

Anaplastic lymphoma kinase (ALK) rearrangement has been identified in approximately 1% of lung squamous cell carcinomas (LUSCCs). Due to its rarity, the efficacy of anaplastic lymphoma kinase-tyrosine kinase inhibitors in the treatment of ALK-positive LUSCCs is poorly characterized.

A 56-year-old female patient with a history of cervical cancer, who had undergone cervicectomy 16 years earlier, presented complaining of shortness of breath for one week. Her chest computed tomography (CT) showed a large right pleural effusion. Fine-needle aspiration of the right hilar lymph node revealed metastatic squamous carcinoma, and the patient was diagnosed with stage IVA LUSCC. Polymerase chain reaction test showed positive for ALK fusion. The patient was started on alectinib and achieved a partial response after 48 days. After two months, chest CT showed progressive disease. Next-generation sequencing analysis of the pleural nodule biopsy showed an EML4-ALK fusion, a CDKN2A mutation (p.F90Lfs*30), and 11q13.3 (CCND1, FGF3, FGF4, and FGF19), CDK4, and MDM2 amplification. The patient received two cycles of nab-paclitaxel and carboplatin, and repeated CT scan showed disease progression. Her treatment was subsequently changed to glumetinib plus iruplinalkib and she died less than one month later.

We reported a rare case of EML4-ALK fusion-positive LUSCC with a short-term response to alectinib and poor survival. Co-amplification of the multiple genes may be involved in aggressive disease and drug resistance, which should be considered in future clinical trials and clinical management. Early broad-panel next-generation sequencing testing in LUSCC patients who are never-smokers may help guide management for patients who have complex mutational profiles.