Brain metastasis incidence with bireociclib in HR+/HER2- advanced breast cancer: Pooled analysis of BRIGHT-1 and BRIGHT-2 study.

e13057 Background: Brain metastases (BM) significantly impact prognosis of patients (pts) with breast cancer (BC). Meta-analysis showed that hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic BC (MBC) had a pooled cumulative BM incidence of 15% with an incidence of 0.05 (95%CI: 0.03–0.08) per patient-year (Kuksis et al, Neuro Oncol 2021). Bireociclib, a novel CDK4/6 inhibitor, demonstrated favorable blood-brain barrier penetration and brain tissue distribution in preclinical study, and pronounced efficacy for HR+/HER2- advanced BC (ABC) in clinical study. Here we report the incidence of BM among pts with HR+/HER2- ABC after bireociclib treatment. Methods: We conducted a pooled analysis of HR+/HER2- ABC pts from BRIGHT-1 (NCT04539496) and BRIGHT-2 (NCT05077449) study. The cumulative incidence of BM was calculated using survival analysis, with incidence defined as events per total patient-years at risk. Results: A total of 697 ABC pts without BM at baseline were pooled for analysis. The baseline characteristics were showed in the table. In the pts receiving bireociclib containing regimens (n = 596), the pooled cumulative incidence of BM was 2.36% with an incidence of 0.0114 (95%CI: 0.0047, 0.0181) per patient-year. Median time from first dose or randomization to onset of BM was 7.36 months (n = 12). In heavily pretreated MBC pts (n = 264), the cumulative incidence of BM and the corresponding incidence per patient-year was 3.15% and 0.0144 (95%CI: 0.0030, 0.0259), respectively. Comparative analysis in the pts who failed prior first-line endocrine therapy revealed that cumulative incidence of BM and incidence per patient-year were 1.36% and 0.0070 (95%CI:0.0000, 0.0149) in bireociclib plus fulvestrant group (n = 297) and 8.16% and 0.0141 (95%CI: 0.0000, 0.0336) in placebo plus fulvestrant group (n = 101), respectively. Conclusions: This pooled analysis demonstrates numerically lower incidence of BM in HR+/HER2- MBC pts treated with bireociclib containing regimens, suggesting bireociclib's potential to reduce BM occurrence and inhibit intracranial lesions in ABC. Clinical trial information: NCT04539496 , NCT05077449 . BIRE treated pts (N=596) BIRE Monotherapy (N=264) BIRE+FUL (N=269) PBO+FUL (N=101) Follow-up time (Md, mo) 24.4 26.9 21.3 18.9 Age (Md, IQR, years) 54 (47, 62) 53 (46, 61) 54 (47, 63) 55 (48, 62) ECOG (0 vs 1, %) 31.2 vs 68.8 28.0 vs 72.0 36.4 vs 63.6 44.6 vs 55.4 HR status (ER+PR+ vs ER+PR-, %) 79.5 vs 18.6 77.3 vs 18.9 79.6 vs 20.1 71.3 vs 28.7 Ki-67 (Md, IQR, %) 30 (15, 40) 30 (15, 40) 30 (15, 40) 25 (10, 40) Visceral mets (liver vs lung, %) 38.4 vs 47.0 51.5 vs 52.3 32.0 vs 41.3 36.6 vs 44.6 Disease setting (locoregional vs metastatic, %) 3.0 vs 97.0 0 vs 100 5.6 vs 94.4 4.0 vs 96.0 Prior ET for metastatic disease (Number of regimens ≤1 vs >1, %) 66.6 vs 33.4 25.0 vs 75.0 99.6 vs 0.4 100 vs 0 Prior chemotherapy for metastatic disease (Number of regimens ≤1 vs >1, %) 79.7 vs 20.3 54.5 vs 45.5 100 vs 0 100 vs 0