Stage IIIA ALK-positive lung adenocarcinoma: pathologic complete response to lorlatinib

What happened, in summary

A 35-year-old man with no symptoms was diagnosed with locally advanced Stage IIIA ALK-positive lung adenocarcinoma after pulmonary nodules found during routine health assessment enlarged over time. He had smoked about 1 pack per day for 15 years and had no family history of hereditary disease or cancer. CT on 15 February 2023 showed a 4.6 x 2.8 cm mass in the left inferior lobe with obstructive changes. PET-CT showed high uptake in the lung mass and in left hilar and mediastinal lymph nodes at stations 4L, 7, and 8, without distant metastasis. Endobronchial ultrasound-guided biopsy confirmed adenocarcinoma. Immunohistochemistry was positive for Napsin A, cytokeratin, TTF-1, and ALK, and next-generation sequencing found an EML4-ALK fusion. The clinical stage was cT2bN2M0. A multidisciplinary team considered the tumor potentially resectable, so he received neoadjuvant lorlatinib 100 mg daily from 7 March to 28 June 2023. CT showed the lesion shrinking to 2.8 x 1.5 cm after 4 weeks and 1.8 x 1.0 cm after 12 weeks, a partial response. On 13 July 2023, he had VATS left inferior lobectomy with mediastinal lymph-node dissection and mediastinal cyst resection. Pathology found no tumor cells in the tumor bed or resected lymph nodes, consistent with pathologic complete response. He continued lorlatinib and remained disease-free at 10 months, with a plan for 3 years of adjuvant therapy. Later side effects included grade 3 weight gain, grade 3 hyperlipidemia improved with ezetimibe and fenofibrate, and sinus tachycardia that normalized with metoprolol.