Final analysis of a non-interventional study on cabozantinib in patients with advanced renal cell carcinoma after prior checkpoint inhibitor therapy (CaboCHECK).

357 Background: Data for cabozantinib after IO-combinations in metastatic renal cell carcinoma (mRCC) remain scarce. We therefore evaluated safety and effectiveness of cabozantinib after failure of IO-based therapies. Methods: Data from patients (pts) with mRCC and cabozantinib treatment after IO-based therapy was retrospectively collected from medical records. Primary endpoint was the incidence of serious adverse events (SAEs). Response rate was assessed clinically (CRR) and/or according to RECIST 1.1. Overall Survival (OS) and Progression Free Survival (PFS) were assessed from start of therapy and data were compared for pts with starting dose of 60 mg (cohort A) vs < 60 mg (cohort B) in a post-hoc analysis. Descriptive statistics and KM-plots were utilized, where appropriate. Results: This final analysis (cut off 08-Oct-21) assessed 56 eligible pts (71.4% male) with median age of 66 yrs. 87.5% (n = 49) had previous nephrectomy. 66.1% (n = 37) had clear cell RCC. 89.3% (n = 50) had ≥2 previous lines. ECOG ≤1 was 33.9% (n = 19). IMDC factors were 0 in 2 (3.6%), ≥1 in 21 (37.5%), missing in 31 pts (55.4%). 62.5% (n = 35) started at reduced dose. 55.4% (n = 31) required dose reductions and 1.8% (n = 1) discontinuation. Median treatment duration was 6.1 months (m). PR was 10.7% (n = 6), SD 19.6% (n = 11), PD 12.5% (n = 7) and missing in 57.1% (n = 32). Median OS and PFS were 15.34 m (95% CI 8.94, 20.93) and 6.34 m (95% CI 5.29, 8.25) in the ITT, 10.48 m (95% CI 6.01, 34.14) and 6.51 m (95% CI 2.99, 10.87) in cohort A and 16.46 m (95% CI 9.56, 23.33) and 6.34 m (95% CI 4.86, 8.71) in cohort B, respectively. All grade AEs and grade 3-5 AEs were 87.5% (n = 49) and 44.6% (n = 25) in the ITT, 95.0% (n = 19) and 55.0% (n = 11) in cohort A and 85.7% (n = 30) and 40.0% (n = 14) in cohort B. SAEs were reported in 21.4% (n = 12) of pts, which were 30.0% (n = 6) of cohort A and 17.1% (n = 6) of cohort B. Treatment related SAEs were reported in 10.7% (n = 6) of pts, which were 15.0% (n = 3) in cohort A and 8.6% (n = 3) in cohort B. Conclusions: Cabozantinib directly after IO therapy was safe and feasible. No new safety signals were reported. A reduced starting dose was frequently utilized and was not associated with adverse outcomes. Our data supports the use of cabozantinib after IO-failure. Major limitation was the retrospective nature of our study.[Table: see text]