Response to treatment with an ALK-TKI in a patient with advanced lung adenocarcinoma with concurrent ALK fusion and high PD-L1 expression: A case report

Abstract

Rationale: Previous studies have shown that PD-L1 TPS ≥50% in lung cancer rarely overlaps with driver oncogenes such as epidermal growth factor receptor and anaplastic lymphoma kinase (ALK). The initial gene detection of the patient in this study showed ALK fusion combined with high expression of PD-L1. We explored the treatment options for this patient. Patient concerns: A 34-year-old woman presented for the first time with “repeated fever and cough for 20 days.” The patient denied any underlying medical history. Diagnosis: After a series of imaging examinations and needle biopsy, the patient was diagnosed as stage IV lung adenocarcinoma with multiple liver and bone metastases (EML4-ALK fusion, PD-L1 TPS 80%). Interventions: The patient was initially given alectinib targeted therapy. After progression, a second round of genetic testing was performed and the patient was detected to have both ALK fusion and BRAF mutation. The patient was then successively changed to treatment with ensatinib combined with dabrafenib, and lorlatinib combined with dabrafenib. Outcomes: The initial efficacy evaluation of alectinib was PR, but its PFS was only 4 months. The patient only achieved an overall survival of 10 months. Lessons: Non–small cell lung cancer with an ALK fusion and high PD-L1 expression responds poorly to most current treatment options, with survival time after ALK-tyrosine kinase inhibitor treatment notably shorter than that of patients with an ALK fusion alone.

HIP1-ALK–Rearranged Lung Cancer in a Young Adult With BRAF V600E Mutation Detected After ALK Tyrosine Kinase Inhibitor Therapy: A Case Report

“…Another study reported that the administration of ensartinib and dabrafenib for the BRAF V600E mutation detected post-alectinib in EML4-ALK–rearranged lung cancer; however, the treatment was discontinued owing to severe adverse events. 6 Further research is needed to address BRAF V600E as a resistance mechanism to ALK TKI. In addition, most studies focused on EML4-ALK, and whether they can be applied to rare variants of ALK-rearranged lung cancers, including HIP1-ALK, needs to be verified.…”