Comprehensive Ethnicity Assessment of Ribociclib Pharmacokinetics in Patients With Early and Advanced Breast Cancer

BACKGROUND: Pharmacokinetics (PK) ethnicity assessment of ribociclib, a selective CDK4/6 inhibitor approved in combination with endocrine therapy for HR+/HER2- early breast cancer (eBC) and advanced breast cancer (aBC), in Asian and global patients is presented. METHOD: PK data were analyzed from six global and three Asian studies: a phase 1 study of advanced solid tumors or lymphomas (X2101), a phase 1b/2 aBC study (X2107), three pivotal phase 3 aBC studies (MONALEESA-2/-3/-7), a pivotal phase 3 eBC study (NATALEE), a Japanese phase 1 study in advanced tumors (X1101), an Asian phase 2 aBC study (MONALEESASIA), and a phase 2 Chinese aBC study (A2206). RESULTS: PK parameters from global and Asian studies were collected. At 600 mg ribociclib, PK exposure (area under the curve, maximum concentration, trough concentration) in Asian studies (MONALEESASIA, A2206) was comparable with that seen in global studies (X2101, X2107, MONALEESA-2/-3/-7) in advanced cancer and aBC. The PK exposure range in Japanese patients in X1101 and MONALEESASIA was largely comparable with that in non-Japanese Asian patients in MONALEESASIA and global patients (X2101) at both 400 and 600 mg doses of ribociclib. Intrastudy analyses of MONALEESA-3/-7 and NATALEE further suggested comparable PK exposure between Asian and non-Asian patients with aBC and eBC. CONCLUSIONS: This comprehensive ethnicity assessment suggests comparable PK of ribociclib between Asian and non-Asian patients and supports current dose recommendations in Asian patients.