Treatment and Attrition Trends for Metastatic Clear Cell Renal Cell Carcinoma in the US.

Importance: The treatment landscape of metastatic clear cell renal cell carcinoma (ccRCC) has rapidly evolved with the approval of multiple immune checkpoint inhibitor (ICI)-based combinations. However, clinical data on changes in treatment patterns and attrition before and after ICI-based combinations approval are lacking. Objective: To assess treatment patterns and attrition rates in patients with metastatic ccRCC before and after the approval of ICI-based combinations. Design, Setting, and Participants: This cohort study used patient-level data from a nationwide deidentified electronic health record-derived database, originating from around 280 cancer clinics in the US. Patients diagnosed with metastatic ccRCC who received first-line therapy between January 1, 2011, and January 20, 2023, were included. Those treated for 2 or more malignant neoplasms or enrolled in clinical trials were excluded. Exposures: Line of therapy initiation before and after April 16, 2018. Main Outcomes Measures: Treatments received in each line of therapy and attrition rate were summarized using frequencies and percentages. Results: Of 12 707 patients with metastatic ccRCC within the database, 8534 were eligible and included (median [IQR] age, 66 [59-74] years; 6032 male [70.7%]; 629 Black [8.1%], 697 Hispanic [9.0%], 5493 White [71.0%]). Before April 16, 2018, the most common first-line therapy was tyrosine kinase inhibitor (TKI) monotherapy (3595 of 4561 patients [78.8%]). Following the approval of ICI-based combinations in 2018, most patients (2392 of 3973 patients [60.2%]) received ICI-based combinations as first-line therapy for metastatic ccRCC. TKI monotherapy remained the most common second- and third-line therapy in patients treated before and after April 16, 2018. Before 2018, 2639 patients (57.9%) and 1458 patients (31.9%) received second-line and third-line therapies, respectively, compared with 1494 (37.6%) and 562 (14.1%) after 2018. Conclusions and Relevance: In this cohort study of 8534 patients with metastatic ccRCC, although ICI-based combinations are the preferred first-line therapy due to their proven superiority over TKI monotherapy, many patients were not receiving them; high attrition rates were observed in subsequent lines. These findings highlight the need to optimize treatment selection by implementing current guidelines in clinical practice.