Clinical impact of early progression among patients (Pts) with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs) in first-line (1L) setting: IMPACT RCC real-world study

e17079 Background: Previous research has indicated a high burden of illness among mRCC pts who progressed to second line (2L) systemic therapy, suggesting benefits to delaying 1L progression. This study examined the clinical impact of early vs delayed disease progression among mRCC pts treated with 1L TKI monotherapies followed by 2L therapy in the US Veterans Health Administration (VHA) database. Methods: Newly diagnosed mRCC pts treated with 1L TKIs followed by 2L therapy were identified between OCT2013-MAR2018 within the VHA database (1L start date = index date). Eligible pts were required to have continuous enrollment for ≥6 months post-2L therapy initiation unless the pt died. A Kaplan-Meier (KM)-derived median time to 2L therapy initiation was used as the cut-off to categorize pts into early (≤median) and delayed ( > median) progression cohorts. KM analysis and Cox proportional hazards models were used to compare and assess the impact of predictive factors on clinical outcomes including overall survival (OS), time to 2L discontinuation (index date to 2L discontinuation or death), and time to 3L treatment initiation (index date to 3L start or death) among pts in the early vs delayed progression cohorts. Results: Among 289 mRCC pts, the mean age was 67.4 years and the median time to 2L initiation was 6.1 months. Pt characteristics were similar between the early (n = 145) and delayed (n = 144) progression cohorts. During follow-up, the delayed progression cohort had better clinical outcomes than the early progression cohort did (Table below). Conclusions: Early progression is associated with worse clinical outcomes, confirming the need to delay disease progression among mRCC pts with effective 1L treatment strategies. Results indicate the need for use of more efficacious therapies, e.g. immuno-oncology-based combinations, in 1L that can delay disease progression and have potential to reduce disease burden. [Table: see text]