Whether AI+CDK4/6i+HP is Suitable Treatment for Three Positive Metastatic Breast Cancer Patient with Renal Insufficiency Caused by Type 2 Diabetes

Abstract

Background: Hormone-receptor positive (HR+) ，ERBB2 gene mutation (HER2+) breast cancer is a very common type of breast cancer, but it is relatively rare for metastatic breast cancer (MBC) who are newly treated and have renal insufficiency. In previous studies, no long-term survival reports have been found for such patients. In order to clarify the above issues, we have innovatively developed a plan that focuses on molecular targeted therapy and endocrine therapy. We reported the results of a breast cancer patient with HR+ and HER2+concurrent renal insufficiency. Although the patient did not have the opportunity to receive surgical treatment and chemotherapy, the results showed that the aromatase inhibitors (AI)+Cyclin D-cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) +trastuzumab & pertuzumab (HP) treatment was also an effective and feasible approach.

Methods: The patient with HR+ HER2-positive MBC with activating HER2 mutation(s) received AI+CDK4/6i+HP (oral letrozole 2.5 mg/day, oral abemaciclib 150mg twice/day with mandatory loperamide prophylaxis for the first 2 cycles and as needed thereafter, and intravenous trastuzumab 8mg/kg initially then 6 mg/kg every 3 weeks plus pertuzumab 840mg initially then 420mg every 3 weeks) therapy. Efficacy endpoints included progression-free survival (PFS) (RECIST v1.1). Secondary endpoints are treatment time, exploratory targets are tumor markers, and safety targets are changes of renal function. Plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing.

Results: The duration of response time lasted for approximately 60 weeks. The treatment time was 81weeks.The PFS was 17.6 months. Responses were observed in patient within 6 weeks. Longitudinal ctDNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA.Throughout the entire treatment cycle, the patient's renal function remained stable, with no significant fluctuations in creatinine, creatinine clearance rate, serum urea, and serum potassium.

Conclusion: AI+CDK4/6i+HP is a safe and effective treatment for patients with three positive metastatic breast cancer patients with renal insufficiency caused by type 2 diabetes. Throughout the entire treatment process, the patient's renal function remains stable. Further investigation is needed.