Efficacy of Treatments After Lenvatinib in Patients with Advanced Renal Cell Carcinoma

We present real-world data on the efficacy of treatments for patients with renal cell carcinoma that progressed on lenvatinib-based therapy. We observed modest activity of tyrosine kinase inhibitor–based therapy after lenvatinib exposure, which underscores the need for better subsequent treatment options. Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) used in the upfront and refractory settings for metastatic renal cell carcinoma (mRCC). However, there are limited data on the efficacy of subsequent TKI therapies after lenvatinib. We investigated the activity of TKI therapies after lenvatinib in patients with mRCC. We conducted a retrospective analysis of data from the International Metastatic RCC Database Consortium (IMDC). Patients who received post-lenvatinib treatment were divided into two cohorts: a second-line cohort after first-line lenvatinib; and a third-line cohort after second-line lenvatinib. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the time to treatment failure (TTF). Of the 168 patients included, 122 (73%) had clear-cell histology. In the second-line cohort (n = 20), all patients received first-line pembrolizumab + lenvatinib. The ORR was 50% and median TTF was 19.7 mo for first-line treatment. Median follow-up from initiation of second-line treatment was 4.9 mo. The ORR to second-line treatment was 5% (95% confidence interval [CI] 0.2–25%) and median TTF was 5.8 mo (95% CI 1.9–14.9). In the third-line cohort (n = 34), most patients received second-line everolimus + lenvatinib (97%). The ORR was 31% and median TTF was 9.2 mo for second-line therapy. Median follow-up from initiation of third-line treatment was 14.9 mo. The ORR to third-line treatment was 12% (95% CI 3.3–27%) and median TTF was 2.8 mo (95% CI 1.9–7.4). Our data demonstrate modest activity of TKI-based therapy after exposure to lenvatinib. The results highlight the need for better treatment options for patients who experience progression on lenvatinib-based therapies. Lenvatinib is a type of drug called a tyrosine kinase inhibitor (TKI). It is used to treat metastatic kidney cancer either when first diagnosed or after progression on a previous treatment. There is limited information on how patients respond to a different TKI after receiving lenvatinib. Our results show that other TKIs have modest clinical activity after patients have received lenvatinib.