Efficacy of post-lenvatinib treatments in patients (pts) with advanced renal cell carcinoma (aRCC).
Authors: Justine Panian, Caiwei Zhong, Sharon Choi, Roxanne Quinn, Evan Ferrier, Eddy Saad, Renee Maria Saliby, Carmel Malvar, Sumanta Kumar Pal, Hedyeh Ebrahimi, Ben Tran, Andrew James Weickhardt, Aly-Khan A. Lalani, Cristina Suárez, Guillermo de Velasco, Ravindran Kanesvaran, Martin Zarba, Toni K. CHOUEIRI, Daniel Yick Chin Heng, Rana R. McKay
Journal: Journal of Clinical Oncology (2024)

4538 Background: Lenvatinib is a tyrosine kinase inhibitor (TKI) that targets both vascular endothelial growth factor (VEGF) receptor and fibroblast growth factor receptor. It has demonstrated efficacy both in the upfront and refractory disease settings. However, there is a lack of data surrounding the efficacy of TKIs post-lenvatinib exposure. In this study, we investigate the activity of post-lenvatinib therapies in pts with aRCC. Methods: We conducted a retrospective analysis utilizing the International Metastatic Database Consortium (IMDC). Pts having received treatment post lenvatinib exposure were eligible and divided into two cohort: pts post-1 st line lenvatinib (2 nd line cohort) and pts post-2 nd line lenvatinib (3 rd line cohort). The primary objective was objective response rate (ORR) and time to treatment failure (TTF). ORR was summarized with 95% two-sided exact binomial confidence interval. TTF was defined as time from treatment initiation to drug cessation for any reason censored at the date of last follow-up. Results: Overall, 84 pts received 1 st line lenvatinib of whom 43 (51%) remain on therapy, 20 (24%) received 2 nd line treatment, and 21 (25%) received no subsequent treatment. All pts received 1 st line pembrolizumab + lenvatinib (ORR 50%, median TTF 9.7 months). Reason for lenvatinib discontinuation was progression (50%), progression + toxicity (20%), toxicity (15%), or other (15%). For the 2 nd line cohort, median age was 61 years, most pts were male (85%), had prior nephrectomy (75%), clear cell histology (85%), and were IMDC intermediate/poor risk (55%). 2 nd line therapy regimens included TKI monotherapy (80%), TKI-IO (5%), and other (15%). The ORR to 2 nd line treatment was 5% (95% CI 0.2-25) and median TTF was 5.8 months (95% CI 1.9-14.9). Of 2 nd line lenvatinib-exposed pts (n=84), 24 (29%) remain on treatment, 34 (40%) received 3 rd line treatment, and 26 (31%) did not receive additional therapy. Most pts received 2 nd line everolimus + lenvatinib (97%) (ORR 39%, median TTF 5.9 months). Reason for lenvatinib discontinuation was progression (59%), progression + toxicity (9%), toxicity (12%), or other (21%). For the 3 rd line cohort, median age was 67 years, most pts were male (68%), had prior nephrectomy (88%), clear cell histology (68%), and were IMDC intermediate/poor risk (77%). 3 rd line treatments included TKI alone (50%), IO-TKI (38%), and other (12%). The ORR to 3 rd line treatment was 12% (95% CI 3.3-27) and median TTF was 2.8 months (95% CI 1.9-7.4). Conclusions: In this analysis, we demonstrate modest activity of TKI-based therapy post-lenvatinib exposure. Our study highlights the need for improved treatment options for pts progressing on lenvatinib-based therapies.