Real-world efficacy and safety of pembrolizumab plus lenvatinib in patients with metastatic renal cell carcinoma: a multi-institutional retrospective study

Sci Rep. 2025 Dec 12;15(1):43676. doi: 10.1038/s41598-025-27578-6.

Abstract

Despite the potential of pembrolizumab and lenvatinib combination therapy in treating metastatic renal cell carcinoma (mRCC), real-world evidence on its efficacy and safety remains limited. We retrospectively analyzed data from 118 patients with mRCC who initiated pembrolizumab plus lenvatinib as first-line therapy between August 2022 and March 2024. Patient characteristics, treatment outcomes, and adverse events were evaluated. Oncological outcomes were stratified following the International Metastatic RCC Database Consortium risk classification. The objective response and disease control rates were 69.5% and 98.5%, respectively. Median progression-free survival (PFS) was 26.8 months (95% confidence interval (CI), 23.5-27.8)), whereas the median overall survival (OS) was not reached (95%CI, 20.5- not reached). Grade ≥ 3 treatment-related adverse events occurred in 39.8% of all patients. Clinical outcomes were also compared between patients aged ≥ 75 and < 75 years. Median age was 70 years; 70.3% and 29.7% aged < 75 and ≥ 75 years, respectively. No significant differences were observed in PFS and OS between the two groups (p = 0.14 and p = 0.44, respectively). Pembrolizumab plus lenvatinib demonstrated favorable efficacy and manageable safety in a real-world cohort of patients with mRCC, including older adults.

Keywords: Immune checkpoint inhibitor; Lenvatinib; Pembrolizumab; Renal cell carcinoma.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / mortality
  • Carcinoma, Renal Cell* / pathology
  • Female
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / mortality
  • Kidney Neoplasms* / pathology
  • Male
  • Middle Aged
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Phenylurea Compounds* / therapeutic use
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Quinolines* / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • lenvatinib
  • Antibodies, Monoclonal, Humanized
  • pembrolizumab
  • Phenylurea Compounds
  • Quinolines