Combination of lenvatinib and pembrolizumab in treatment of patients with metastatic renal cell carcinoma and factors of poor prognosis

Renal cell carcinoma (RCC) are among the most frequently diagnosed types of cancer in the world. Despite improvements in diagnostics in the recent years, every third patient with RCC is still diagnosed at the metastatic stage, which explains high mortality rates with this pathology. RCC is a heterogeneous disease. At the stage of metastatic process, factors including presence and site of metastases, prior nephrectomy before systemic therapy, and sarcomatoid differentiation based on the pathomorphological study are most important in determining treatment tactics.

In the era of cytokine therapy, patients with metastases were treated with cytoreductive nephrectomy as a first step, as demonstrated in the SWOG and EORTC trials. Currently, the National Comprehensive Cancer Network (NCCN) Guidelines, European Society for Medical Oncology (ESMO) Guidelines, and American Urological Association (AUA) Guidelines suggest a more selective approach to cytoreductive nephrectomy in patients with metastatic RCC and selection of patients for surgery according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. And for poor prognosis group, preference should be given primarily to dual immune or immune-targeted systemic therapy. Surgical intervention is reserved for patients with not more than 3 factors, with “low metastatic load”, and good performance status.

This publication describes a clinical case of successful treatment of a 58-year-old patient with metastatic RCC (T3bN1M1) and poor prognosis according to the IMDC criteria. The patient had no prior history of nephrectomy and presented with a venous tumor thrombus of the right renal vein and the inferior vena cava up to the level of the caval porta, along with metastases to the liver and the 10th thoracic vertebra.

The combination of lenvatinib and pembrolizumab was selected as first-line therapy and administered from February 2023 to March 2025 (25 months of treatment).

After 3 months of lenvatinib plus pembrolizumab treatment, the tumor thrombus showed reduction (began to be washed by blood), and disease regression was reported in the form of a 60 % reduction in target lesions per the RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) criteria. Most notably, the liver metastasis demonstrated a remarkable decrease from 7 cm to 2 cm (>78 % reduction), which was achieved with the therapy conducted. The tumor of the right kidney exhibited a >50 % size reduction (from 10 cm to 5 cm), accompanied by decreased contrast enhancement in the aortic phase on imaging.

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