PS-BPR02-1: A CASE OF ADVANCED ENDOMETRIAL CANCER AFTER NEPHRECTOMY FOR RENAL CELL CANCER WITH HYPERTENSION AND PROTEINURIA INDUCED BY LENVATINIB

Abstract

Background: The combination of pembrolizumab plus lenvatinib is approved for advanced endometrial cancer that is not MSI-H or dMMR, is progressive on prior systemic therapy, and is not amenable to curative surgery or radiation. Lenvatinib is an oral, multi-targeted tyrosine kinase inhibitor (TKI) that exerts anti-malignant effects by inhibiting many tyrosine kinase receptors, such as VEGF receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, rearranged during transfection (RET), and stem cell factor receptor (KIT) signaling networks. Although lenvatinib's usefulness has been demonstrated, adverse effects such as hypertension and proteinuria often necessitate the discontinuation of administration. We encountered a patient with advanced endometrial cancer after nephrectomy for renal cell cancer who developed hypertension and proteinuria due to lenvatinib. We discussed TKI induced hypertension and proteinuria in patients on pre-existing eGFR decline. Case presentation: A 65-year-old Japanese female was diagnosed in 2011 with concurrent endometrial cancer and right renal cell cancer. She underwent total hysterectomy, bilateral salpingo oophorectomy, and right nephrectomy. She received 6 courses of CAP (cyclophosphamide, epirubicin and cisplatin) therapy as adjuvant chemotherapy for endometrial cancer. More than 7 years later, the patient presented with a vaginal cuff recurrence that was histologically confirmed and radiotherapy was indicated. In 2019, there was a recurrence in pelvic lymph nodes. Between 2019 and 2021, she underwent 9 cycles of chemotherapy with carboplatin plus paclitaxel, however the cancer progression was observed. In February 2021, the patient was started on pembrolizumab and Lenvatinib (20 mg/day) combination therapy. Her creatinine was 0.85 mg/dL, with an eGFR of 52 mL/min/1.73m2 before the administration of lenvatinib. The patient experienced continuous grade 3 hypertension (systolic blood pressure Hiragino Sans 160 mmHg or diastolic blood pressure ≧ 100 mmHg), and 2 antihypertensive agents(amlodipine and ormesartan) were required to control hypertension. Despite lenvatinib dose reduction and the aggressive use of antihypertensive agents, grade 3 hypertension had recurred several times, and then proteinuria gradually increased to 3.0 g/day. Lenvatinib was decreased to 10 mg/day (2 steps of dose reduction) within 2 months of treatment initiation, and finally, hypertention and proteinuria were ameliorated. Conclusion: A history of nephrectomy, pre-existing eGFR decline and hypertension are associated with developing TKI induced proteinuria. These patients should be monitored carefully, and appropriate measures for the early control of hypertension and proteinuria may result in higher-dose treatment with lenvatinib, thereby maximizing its therapeutic effect.