Ji, Yan, Yartsev, Vitaly, Quinlan, Michelle, Serra, Paolo, Wang, Yingbo, Chakraborty, Abhijit and Miller, Michelle (2023) Ribociclib Dose Justification in Advanced Breast Cancer Patients With Renal Impairment by Integrating PK, Safety and Efficacy Data. Clinical pharmacokinetics.

Abstract

Background: Renal impairment (RI) is common in cancer patients and can alter the pharmacokinetics (PK) and thus the safety and efficacy of drugs. We assessed the impact of RI during treatment with ribociclib, a cyclin-dependent kinase 4/6 inhibitor, and determined dose recommendations for advanced breast cancer (ABC) patients with RI.
Methods: A comprehensive assessment integrating PK, safety and efficacy data from a phase I RI study in non-cancer subjects and six phase I–III trials in cancer patients was performed.
Results: Ribociclib showed higher PK exposure in subjects with RI than those with normal renal function following a single 400 mg dose in the RI study. However, in the clinical trials, both single-dose and steady‑state exposure of ribociclib was comparable between cancer patients with mild/moderate RI and those with normal renal function following the recommended starting dose of 600 mg. Model-predicted steady‑state exposure in ABC patients was also similar across the renal function groups. Progression-free survival was similar and safety profiles were generally consistent across the renal cohorts (normal/mild/moderate) in ABC patients with low-grade and manageable adverse events, demonstrating a positive benefit-risk profile.
Conclusion: From the collective evidence and considering real-world clinical setting, no dose adjustment is recommended for patients with mild/moderate RI, whereas a reduced dose is recommended for patients with severe RI. This report presented a holistic strategy to determine dose in patients with RI and demonstrated the effectiveness of integrating the data of both clinical pharmacology study and patient trials to justify doses in patients with RI.

Item Type:	Article
Date Deposited:	04 Apr 2023 00:45
Last Modified:	04 Apr 2023 00:45
URI:	https://oak.novartis.com/id/eprint/48131