Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM.

Abstract

644 Background: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy. Methods: Russian multicenter observational study included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23-73) years, a male-to-female ratio - 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8%)). More than 2 lines of previous treatment were administered in 45 (61.6%) cases. Most patients were diagnosed with multiple metastases (71 (97.3%)) in >1 site (61 (83.6%)). Nephrectomy was performed in 87.7% (64/73) of cases. At the combined therapy start ECOG PS 2-4 was registered in 16 (20.5%), poor prognosis according to IMDC score – in 33 (45.2%) patients. Median follow-up was 9.7 (1-26) months. Results: objective response rate was 11% (8/73); tumor control was reached in 93.2% (68/73) of cases. Median objective response duration was 10.5 (4.3-16.8) months, tumor control duration – 10.0 (2.5-17.5) months. Median progression-free survival (PFS) achieved 16.9 (95% confidence intervals (CI): 12.1-20.6), overall survival (OS) – 20.8 (95% CI: 15.7-25.9) months. Any adverse events (AE) developed in 83.6% (61/73), AE grade 3-5 - in 23.3% (17/73) of cases. Most frequent AE grade 3-4 were diarrhea (10 (13.6%)) and arterial hypertension (6 (8.2%)). Unacceptable toxicity demanded treatment cancellation in 4.2% (3/73), therapy interruption – in 30.1% (22/73) and dose reduction – in 32.9% (24/73) of patients. Conclusions: unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with lower objective response rate, similar survival and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.

Phase 1 trial of vorolanib (CM082) in combination with everolimus in patients with advanced clear-cell renal cell carcinoma

“…In the randomized, phase 2 Study, patients were randomized to three treatment arms: lenvatinib-everolimus, lenvatinib alone, and everolimus alone, which showed the longest median PFS at 14.6 months in the lenvatinib-everolimus arm in the second-line setting [30]. Moreover, median PFS achieved 16.9 (95% CI: 12.1À20.6) in unselected patients with metastatic renal cell carcinoma (mRCC) treated with lenvatinib with everolimus [49]. These findings suggested that the validity of targeted strategies should not be overshadowed by immunotherapies, combinations can achieve good results.…”