Efficacy of the combination of lenvatinib with pembrolizumab in patients with advanced renal cell carcinoma
Authors: Volkova M. I. , Kalpinskiy A. S. , Goncharova О. A. , Menshikov К. V. , Stativko O. A. , Karabina E. V. , Dergunov A. S. , Polshina N. I. , Aleksandrova E. N. , Lebedinets A. A. , Panov A. K. , Sultanbaev A. V. , Usynin E. A. , Volkonsky M. V. , Mikhalyuk V. V. , Zukov R. A. , Anzhiganova Yu. V. , Gusniev M. A. , Igumnova E. N. , Kuzmicheva S. V. , Pokataev I. A. , Olshanskaya A. S. , Pervakova N. I. , Parsadanova E. L. , Sannikova T. A. , Bystrov A. A. , Dubovichenko D. M. , Mukhitova M. R. , Chubenko V. A. , Shkret K. A. , Gorshenina M. N. , Semenov A. V. , Davlatova M. K. , Kosareva A. E. , Lutoshkina O. A. , Maslova O. A. , Makhnutina M. V. , Mishina A. V. , Murzalina M. Zh. , Podyacheva O. A. , Kalinin S. A. , Mailyan O. A. , Safarova A. R. , Semenova K. O. , Strokova M. A. , Urashkina E. Yu. , Shmygina O. S. , Novikova O. Yu. 
Published: November 2024

Objective: to re-evaluate the efficacy and safety of lenvatinib with pembrolizumab in unselected Russian renal cell carcinoma (RCC) patients, included in the phase IV study, in a median follow-up extended to 17.1 months. The primary end point was progression-free survival (PFS), secondary end points were overall survival (OS), objective response rate (ORR) and duration of response (DOR), disease control rate (DCR) and its duration, as well as safety.

Materials and methods. The study included medical data of 165 patients with verified advanced RCC who received lenvatinib with pembrolizumab in 36 centers of the Russian Federation from 05.02.2018 to 25.07.2024. The median age was 60 (20–76) years, the male to female ratio was 2.3:1. The majority of patients had Karnofsky performance status ³80 % (74.6 %), clear cell RCC (93.3 %) without sarcomatoid differentiation (93.3 %), metachronous metastases (50.9 %) localized in >1 organ (75.2 %), were nephrectomized (63.0 %) and did not receive antitumor therapy (91.0 %). At the time of lenvatinib with pembrolizumab therapy start 40 patients (24.2 %) were classified into International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable prognostic group, 92 (55.8 %) in the intermediate prognostic group, and 33 (20.0 %) in the poor prognostic group. The median follow-up was 17.1 (1.5–72.9) months.

Results. The median PFS achieved 24.0 (18.7–29.3) months, 17-month PFS 60.5 %. The median OS was 48.9 (18.5– 79.2) months, 17-month OS – 76.1 %. Objective response was registered in 46.0 % of patients including 2.4 % complete responders; the DCR was 92.1 %. The median DOR was 16.6 (2.1–72.9) months, duration of disease control –

14.3 (2.1–72.9) months. Confirmed dynamics of change in the sum of tumor foci diameters was recorded in 152 patients, while the median change was –25 % (from –100 % to +29 %). Any decrease in the sum of tumor foci diameters occurred in 69.1 % of cases. The incidence of any adverse events (AE) was 78.2 %, severe AE – 24.2 %, and serious AE – 9.7 %. Immune-mediated AEs developed in 17.0 % of cases and AE grades 3–4 in 6.7 % of cases. Mortality from AEs was 1.2 %.

Conclusion. Compared with the registration study, in real-world clinical practice in patients with advanced RCC the lenvatinib with pembrolizumab provides a lower ORR with comparable PFS and OS rates and demonstrates a satisfactory safety profile.