Abstract 284P
Background
Combination of lenvatinib and pembrolizumab has shown the highest rates of objective response and disease-free survival among the immune-targeted therapies for first-line treatment of metastatic renal cell cancer (mRCC). Recent update of the CLEAR trial has shown no overall survival (OS) benefit for International mRCC Database Consortium (IMDC) favorable and intermediate risk. However, the IMDC model doesn’t consider the volume of metastatic disease and rare histology types.
Methods
Our prospective observational study included pts with mRCC with high burden of disease and clinically meaningful symptomatic metastases who initiated first-line therapy with pembrolizumab and lenvatinib since 2022 to 2024. The primary endpoint was objective response rate (ORR), the secondary end-points were progression-free survival (PFS) and OS.
Results
In total 54 pts were included. Clear cell carcinoma was presented in 43 (79.6%) pts, papillary– in 8 (14.8%) and chromophobe RCC in 3 (7.4%) pts. IMDC intermediate risk was defined in 32 (59.3%), poor – in 21 (38.9%) cases. At the start of treatment 7 pts (13.0%) had Karnofsky score (KS) of 60 or below and 18 pts (33.3%) – 70. Bone metastases were present in 48.1%, liver metastases – in 37% of cases. The number of metastatic sites was ≥3 in 27 pts (50.0%). Complete response was achieved in 1 (2%), partial response - in 18 (36%), stable disease – in 27 (54%), and progressive disease - in 4 (8%) of 50 eligible pts. ORR was 38%, disease control rate – 92%. ORR was consistent in pts with non-clear cell RCC (40%), while in pts with KS ≤60 and pts older than 65 years ORR was low – 16,7% and 20%, respectively. Median depth of response was -25% (-100% to +28%). With a median follow-up time of 9.4 months the 9-month PFS was 61.3%, 9-month OS – 73%. At the time of analysis 20 pts (37%) discontinued treatment: 14 (25.9%) – due to progressive disease, 6 (11.1%) – due to adverse events. Grade 3-5 toxicity was observed in 31 (57.4%) pts (including 2 deaths).
Conclusions
Lenvatinib and pembrolizumab showed clinically meaningful efficacy in pts with bulky metastatic disease and non-clear cell histology. Older age and poor performance status were associated with lower response rate.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.