HER2-targeting antibody-drug conjugate RC48 alone or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma: a multicenter, real-world study.

BACKGROUND: Phase II trials showed the efficacy of anti-HER2 RC48-ADC (disitamab vedotin) for HER2-positive metastatic urothelial carcinoma (UC). This study evaluated RC48 alone verses in combination with immunotherapy for locally advanced or metastatic UC using real-world data. METHODS: This retrospective, multicenter, real-world study included patients with locally advanced or metastatic UC who received RC48 in five hospitals in China between July 2021 and April 2022. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. RESULTS: Thirty-six patients were included. The patients were 47-87 years, and 26 (72.2%) were male. Eighteen patients received RC48 alone, and 18 received RC48 combined with a programmed death-1 antibody. The median PFS was 5.4 months. The median OS was not reached. The 6-month and 1-year PFS rates were 38.8% and 15.5%, respectively. The 1-year OS rate was 79.6%. Fourteen (38.9%) patients achieved a partial response, and the ORR was 38.9%. Eleven patients had stable disease, and the DCR was 69.4%. The median PFS for patients who received RC48 combined with immunotherapy and those who received RC48 alone was 8.5 and 5.4 months, respectively. The main treatment-related adverse events included anemia, hypoesthesia, fatigue, and elevated transaminase. No treatment-related death occurred. CONCLUSION: RC48 alone or combined with immunotherapy might benefit patients with locally advanced or metastatic UC, regardless of impaired renal function.

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.