Real-World Outcomes in Patients with Advanced/Metastatic Renal Cell Carcinoma Receiving Cabozantinib or Other Tyrosine Kinase Inhibitors After Checkpoint Inhibitor-Based Therapy

Abstract

BACKGROUND: Checkpoint inhibitor (CPI)-based therapy is recommended for first-line treatment of advanced/metastatic renal cell carcinoma (mRCC). Cabozantinib is a tyrosine kinase inhibitor (TKI) approved in the USA for treating mRCC, including after CPI-based therapy. However, data on the benefits of subsequent TKI therapy are limited. OBJECTIVE: To study the real-world use and outcomes of cabozantinib versus other TKIs after CPI-based therapy for mRCC. METHODS: This retrospective study used data from the US Oncology Network electronic health record database supplemented by chart review. Patients initiated TKI therapy between 2016 and 2021 after CPI-based therapy. The primary endpoint was real-world response rate in the first 6 months of treatment (RR-6m; physician assessment). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Covariates were adjusted by inverse probability of treatment weighting. RESULTS: Of 485 included patients, 331 received cabozantinib and 154 another TKI. Baseline characteristics were generally similar between arms. For cabozantinib versus other TKIs, adjusted RR-6m (available for 69.3% of patients) was 62.5% versus 46.0% (rate difference: superiority, 16.5% [95% CI: 7.8–25.1], p = 0.0002), adjusted ORR was 62.4% versus 49.4% (p = 0.0020), adjusted median OS was 19.2 versus 19.1 months (p = 0.7353) and adjusted median PFS was 7.9 versus 9.2 months (p = 0.8752). CONCLUSIONS: Cabozantinib following CPI-based therapy was effective for treating mRCC in the US real-world setting. Differences in adjusted RR-6m and ORR significantly favored cabozantinib versus other TKIs. The lack of OS difference may reflect differences in post-index therapy.