Cabozantinib (C) exposure-response (ER) modeling of efficacy and safety endpoints as a function of clearance in patients (pts) with renal cell carcinoma (RCC).

645Background: C is approved for the treatment of advanced RCC after prior antiangiogenic therapy at 60 mg qd with dose reductions to 40 mg and 20 mg used to manage adverse events (AEs). In this study, ER analyses were used to evaluate the effect of C dose on progression-free survival (PFS) and safety endpoints at different apparent clearance (CL/F) values for pts in the phase 3 METEOR study (NCT01865747). Methods: Predicted steady-state C exposures were calculated for doses of 60, 40, and 20 mg in pts with CL/F values of 1.3, 2.23, and 3.3 L/hr; these values were based on population PK models and represent pts with low, average, and high CL/F, respectively. Time-to-event Cox proportional hazard ER models were used to characterize the relationship between predicted C exposure and the probability of PFS and 4 common C AEs: fatigue/asthenia (grade ≥3), palmar-plantar erythrodysesthesia (PPE; grade ≥1), diarrhea (grade ≥3), and hypertension (systolic BP > 160 mmHg or diastolic BP > 100 mmHg). Results: Among ...