140P - Lenvatinib + everolimus in mRCC that has progressed on immunotherapy: A real-world single center experience

Background

The 1^st line treatment of metastatic renal cell carcinoma (mRCC) is either immuno-oncology drug (IO) with IO or IO + vascular endothelial growth factor - tyrosine kinase inhibitors (VEGF-TKIs). At progression, the 2^nd line options are lenvatinib + everolimus (L+E) or cabozantinib which is based on older data from 1^st line TKI era. The best treatment for patients who progress on 1^st line IO combination is not clear. In this study, we report the efficacy and safety of (L+E) in patients with mRCC who progressed on IO + TKI combination.

Methods

This is a retrospective study of mRCC patients, treated at our center from October 2018 to June 2022 who had disease progression after IO + TKI combination. Patients were started on lenvatinib 18 mg and everolimus 5mg per day. As initial patients could not tolerate this dose, after 5 patients, the dose of lenvatinib was reduced to 14mg, with further dose adjustments according to tolerance.

Results

Of the 23 patients in our study; 4 were females and 19 were males. The median age was 54 years. 17 (73.9%) had intermediate risk and 6 (26.1%) had poor risk disease as per IMDC criteria. 11 (47.8%) received L+E as 2^nd line, and 12 (52.2%) as 3^rd line or beyond. 9 (39.1%) patients had partial response (PR), 9 (39.1%) had stable disease while 5 (21.8%) had progressive disease. Overall response rate was 39.1% and disease control rate was 78.2%. Median progression free survival (PFS) was 10 months while median overall survival (OS) was not reached. The overall survival rate at 1 year was 57.1%. 10 patients completed 1 year and 3 patients completed 2 years of treatment without progression, with the longest follow-up being 41 months. 4 patients showed PR even as 3^rd line therapy after progressing on IO combination. Notable grade 3 adverse events were hypertension - 4 (17.4%), mucositis - 3 (13%), diarrhoea - 3 (13%) and hand-foot syndrome - 2 (8.6%) while lesser grades of dysphonia, fatigue and skin rash were seen. Only 2 patients continued on lenvatinib 18 mg, while the rest required dose reduction.

Conclusions

In this real-world experience, L+E showed substantial clinical activity in pre-treated mRCC patients, even after disease progression with IO combination. L+E combination is well tolerated with appropriate dose adjustment of lenvatinib.

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.