Stage IIIA double ALK-fusion lung adenocarcinoma: major pathological response to neoadjuvant alectinib

What happened, in summary

This 58-year-old man had no cough, sputum, hemoptysis, chest pain, or shortness of breath when a physical examination in April 2020 led to chest imaging. He had smoked 20–40 cigarettes per day for more than 7 years but had quit nearly 30 years earlier. Contrast-enhanced CT showed a 4.0 × 3.4 cm mass in the right lower lung and swollen fused hilar and mediastinal lymph nodes. CT-guided biopsy confirmed lung adenocarcinoma, and immunohistochemistry was positive for Napsin A and TTF-1. On 2 May 2020, the diagnosis was confirmed as Stage IIIA lung adenocarcinoma, T2aN2M0. Next-generation sequencing found 2 ALK fusions: ELMOD3-ALK E8:A20 with 41.23% abundance and EML4-ALK E13:A20 with 68.21% abundance. ALK rearrangement was also confirmed by Ventana D5F3 immunohistochemistry. After multidisciplinary discussion, his team chose neoadjuvant alectinib instead of preoperative chemotherapy or radiation. He started alectinib 600 mg twice daily on 20 May 2020. After more than 4 months, CT showed marked shrinkage of the lung tumor to about 1.1 × 0.6 cm and no lymph node enlargement; tumor markers CEA, NSE, and CA19-9 also dropped, and the response was classified as partial response. On 15 October 2020, he underwent sublobar resection of the right lower lobe with systematic mediastinal lymphadenectomy. Pathology showed less than 7% residual tumor tissue, a major pathological response, and all resected nodes were negative. As of April 2025, he had continued adjuvant alectinib for 4 years, with no recurrence, no serious drug-related toxicity, and ongoing clinical follow-up.