49P - Ethnicity assessment of ribociclib pharmacokinetics in advanced breast cancer patients

Background

Ribociclib is an orally bioavailable, highly selective CDK4/6 inhibitor approved for HR+/HER2– advanced or metastatic breast cancer (aBC) treatment in combination with endocrine therapy (ET). Ethnicity assessment of pharmacokinetics (PK) of ribociclib as a single agent or in combination with ET (letrozole, anastrozole or fulvestrant) in Asian and global non-Asian patients are presented.

Methods

PK data from five global studies and three Asian studies were analyzed. Global studies include single-agent Phase I study in advanced solid tumors or lymphomas (CLEE011X2101), Phase Ib/II study (CLEE011X2107) and 3 pivotal Phase III studies (MONALEESA [ML] -2/-3/ -7) of ribociclib+ET in aBC. Asian studies include Phase I single-agent Japanese study in advanced tumors/lymphomas (CLEE011X1101), Phase II Asian study (CLEE011A2115C) and Phase II Chinese study (CLEE011A2206) of ribociclib+ET in aBC. PK parameters, maximal concentration post dose (C_max), area under concentration curve (AUC) and trough concentration (C_trough) of Cycle 1 Day 1 and steady state, were calculated.

Results

At the 600 mg ribociclib dose, mean C_trough showed no apparent difference in Asian vs non-Asian patients in Studies ML-3 and -7, AUC and C_max in Asian patients (A2115) were comparable with non-Asian patients (X2101 and X2107), and C_trough in Asian patients (A2115) were comparable with non-Asian patients (ML-2/-3/-7). Mean ribociclib concentrations were 5-48% higher in Chinese patients than patients in global studies, however, the differences were small and variable, and not considered clinically relevant accounting for ribociclib PK variability and inter-study variabilities. Mean PK exposure (AUC and C_max) in Japanese patients (X1101) was 27%-117% higher than Caucasian patients (X2101), however, the range was within that of Caucasian patients (X2101). In addition, at 400 mg dose, PK exposure (AUC, C_max and/or C_trough) in Japanese patients was comparable to non-Japanese Asian patients (A2115) and global patients (the sample size in A2115 was small).

Conclusions

Considering ribociclib PK variability and inter-study variabilities, PK exposure of ribociclib were largely comparable between Caucasian and Asian patients with aBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

F. Sun, M. Sato, Y. Bi, J.P. Zarate, Y. Ji: Financial Interests, Personal, Full or part-time Employment, Dr. Sun reports other from Novartis, outside the submitted work: Novartis.