The combination of lenvatinib and pembrolizumab in the treatment of patients with metastatic kidney cancer and factors of poor prognosis: experience of clinics in Moscow: A prospective observational study

Background. Combination therapy is the standard of care for intermediate and poor prognosis metastatic renal cell carcinoma. In the IMDC prognostic classification, tumor stage and histological type are not considered due to the lack of independent impact on overall survival. The CLEAR study demonstrated the efficacy of lenvatinib and pembrolizumab combination in long-term treatment outcomes, including overall survival in poor prognosis compared to sunitinib. The KEYNOTE-B61 study demonstrated high efficacy of this combination in patients with non-clear cell renal cell carcinoma. Aim. To evaluate the efficacy of the combination of lenvatinib and pembrolizumab in patients with high tumor burden and non-clear cell histotypes. Materials and methods. This prospective observational study included 54 patients with metastatic renal cell carcinoma who received a combination of lenvatinib and pemrolizumab in the first line between 2022 and May 2024 in oncology clinics of the Moscow Department of Health. Clear cell histotype was represented in 79.6% of cases, 14.8% had papillary cancer, and 5.6% of patients had chromophobe cancer. The primary endpoint was the objective response rate. Results. The objective response was assessed in 50 patients. The objective response rate was 38%, including 2% complete response according to RECIST 1.1, disease progression was in 8% of patients. The median depth of response was -25% (from -100% to +28). The median time to response was 12.4 weeks (1.1–38.3). Conclusion. The efficacy of the combination of lenvatinib and pembrolizumab in real-life clinical practice outside the inclusion criteria of the CLEAR study is clinically significant and allows us to expect improvement even in patients with a large volume of metastatic process and non-clear cell histotype, but the expected benefit in patients with unsatisfactory somatic status remains disputed.