ALK-rearranged Stage IVA lung adenocarcinoma: partial response to pembrolizumab as eighth-line treatment

What happened, in summary

This 70-year-old man was referred after a chest X-ray showed a lung shadow. He had smoked 1 pack per day for 30 years and had hypertension and chronic kidney disease. CT showed a 35 mm mass in the left lower lobe, with enlarged left hilar and mediastinal lymph nodes. PET/CT showed FDG uptake in the lung mass and nodes, and transbronchial lung biopsy diagnosed adenocarcinoma. Brain MRI showed a right temporal lobe metastasis. The lung cancer was staged cT2aN3M1b, Stage IVA. Biomarker testing showed strong ALK staining by immunohistochemistry, scored 3+, and ALK rearrangement was confirmed by fluorescence in situ hybridization. PD-L1 expression was high at 95%. First-line alectinib 600 mg/day led to clinical improvement and partial response, but the left lower-lobe tumor increased 14 months later. He then received multiple later treatments: brigatinib, carboplatin plus pemetrexed, lorlatinib, tegafur/gimeracil/oteracil potassium, alectinib again, and docetaxel. Despite these lines, the left lower-lobe mass gradually enlarged, and CT showed a 40 mm mass. Pembrolizumab was then started as eighth-line treatment. After 2 cycles, the tumor shrank and the response was classified as partial response. Nine months later, he was still maintaining that partial response. The key clinical picture is ALK-rearranged lung adenocarcinoma with brain metastasis and high PD-L1 expression, with pembrolizumab used late after several ALK-targeted therapies and chemotherapy regimens had stopped controlling the disease. The late response was notable because immune checkpoint therapy is not usually the first strategy for ALK-positive disease, especially after multiple targeted therapies have already been used.