Neoadjuvant Lorlatinib Induces Pathological Complete Response in Advanced ALK-Positive Lung Cancer: A Case Report

Objective: Unusual or unexpected effect of treatmentBackground: Chemotherapy has been the conventional treatment method for advanced non-small-cell lung cancer (NSCLC). Nevertheless, the identification and comprehension of oncogenic driver alterations have paved the way for tar-geted therapies, significantly enhancing patient outcomes. The management of locally advanced NSCLC that is positive for ALK presents a challenge due to the lack of reported randomized controlled trials. The efficacy of neoadjuvant and adjuvant targeted therapy in this context remains uncertain.Case Report: A 54-year-old man was diagnosed with stage IIIB (pT1N3M0) upper right lung adenocarcinoma carrying the EML4-ALK fusion gene. Clinically, the patient had multiple enlarged lymph nodes in the right hilum and mediastinum, with the largest measuring approximately 28x19 mm by CT scan and we found that the L4 lymph node was invaded by metastasis. Then, the patient received 1 cycle of chemotherapy with paclitaxel in com-bination with nedaplatin and subsequently received maintenance treatment involving lorlatinib. Two months later, clinical evaluations revealed progressive reduction of the lesions, especially the reduced size of the mediastinal lymph nodes. Therefore, the patient underwent thoracoscopic partial lobectomy and lymphadenectomy and achieved pathological complete response (pCR). After 3 months, a follow-up CT scan was similar to the first postoperative CT scan and no tumor was found.Conclusions: This case demonstrates the potential advantage of lorlatinib as a neoadjuvant therapy in advanced ALK-positive NSCLC. It emphasizes the importance of identifying new therapeutic targets by next-generation sequencing (NGS) and implementing precise treatment strategies in clinical practice.