Lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: an initial Russian experience

Objective: a preliminary assessment of safety, tolerability, and efficacy of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) resistant to antiangiogenic targeted therapy.

Materials and methods. We analyzed medical data of 19 consecutive mRCC patients received lenvatinib in combination with everolimus following antiangiogenic targeted therapy failure. Median age was 55 (23–73) years. ECOG PS 0–1 was in 11 (57.9 %), ECOG 2–4 – in 8 (42.1 %) cases. Four (21.1 %) patients were distributed into the good, 10 (52.6 %) – into the intermediate, and 5 (26.3 %) – into the poor IMDC (International Metastatic Renal Cancer Database Consortium) prognostic group. Multiple metastases were diagnosed in 18 (94.7 %), multiple metastatic sites – in 17 (89.5 %), liver metastases – in 6 (37.6 %) cases. All the patients were previously treated with 1–4 lines  of therapy (≥2 – 12 (63.1 %)). Median follow-up was 5 (2–10) months.

Results. By the time of the analysis 12 (63.2 %) patients are being treated, 7 (36.8 %) – completed combined treatment (due to RCC progression – 4 (21.1 %), toxicity – 2 (10.5 %), death from unrelated reason – 1 (5.3 %)). Median time of completed therapy was not reached, mean treatment time was 5.1 (1.9–11.2) months. Adverse events were registered in 17 (89.5 %) patients (grade III – 3 (15.8 %), grade IV – 0, grade V – 1 (5.3 %)). The most common adverse events were diarrhea (68.4 %), stomatitis (57.9 %), hypertension (42.1 %), and weight loss (47.4 %). Lenvatinib or everolimus dose reduction was demanded in 5 (26.3 %) and 0, therapy interruption – in 5 (26.3 %) and 1 (5.3 %) patient respectively. Maximal response was assessed as partial in 1 (5.3 %) and stabilization – in 18 (94.7 %) cases. Decline of metastases size was registered in 12 (63.2 %) (median – 17 % (3–40 %)), stabilization – in 8 (42.1 %), enlargement – in 1 (5.3 %) patient. Median time to maximal response was 2 (2–4) months. Five-months overall and progression-free survival rates were 76.1 and 87.4 % respectively. Following 2 cycles of combined therapy ECOG PS improved in 11 (57.9 %), stabilized – in 6 (31.6 %), worsened – in 2 (10.5 %) patients.

Conclusion. Our preliminary data have confirmed antitumor activity and showed acceptable tolerability of lenvatinib in combination with everolimus in unselected patients with mRCC resistant to antiangiogenic targeted therapy.