Pralsetinib for the treatment of a RET-positive advanced non-small-cell lung cancer patient harboring both ANK-RET and CCDC6-RET fusions with coronary heart disease: a case report

Background: Rearranged during transfection (RET) is one of the rare driver genes of non-small-cell lung cancer (NSCLC), having a gene fusion incidence of 1-2% in NSCLC. Before the emergence of specific RET inhibitors, multikinase inhibitors such as cabozantinib and vandetanib were tried for RET fusion-positive NSCLC, but their efficacies were poor, and the U.S. Food and Drug Administration did not approve the application of these drugs for such patients. In the phase I/II ARROW clinical trial, pralsetinib significantly improved the overall remission rate and disease progression-free survival (PFS) of RET fusion-positive NSCLC patients. In the clinic, it is necessary to conduct adequate molecular screening of patients to guide drug choices. With the wide application of second-generation sequencing technology in clinical practice, many RET fusion partners have been discovered. It is rare for one patient with two RET fusions.

Case description: This paper reports a rare case of RET dual fusion in an advanced NSCLC patient who had coronary heart disease. After the failure of first-line treatment with platinum-based chemotherapy and post-line treatment with small-molecule targeted therapy of anlotinib and alectinib, the application of pralsetinib (400 mg, qd) reduced the tumor volume by 79% and achieved partial remission (based on the evaluation criteria of the World Health Organization) or reduced tumor volume by 17% (based on the Response Evaluation Criteria in Solid Tumors). It had an overall manageable safety profile.

Conclusions: This patient with two different RET fusions was sensitive to pralsetinib. Patients with well-controlled coronary heart disease and recurrent myocardial infarction might benefit from pralsetinib. The pathogenesis of RET-dual-fusion NSCLC and its clinical impact need to be further studied to provide a theoretical basis for personalized treatment.