Bireociclib plus fulvestrant for advanced HR<sup>+</sup>/HER2<sup>-</sup> breast cancer progressing after endocrine therapy: Interim analysis of a phase 3 trial (BRIGHT-2).
Authors: Jiayu Wang, Qingyuan Zhang, Huiping Li, Zhongsheng Tong, Quchang Ouyang, Huihui Li, Yuee Teng, Biyun Wang, Tao Sun, Jingfen Wang, Wei Li, Zhaofeng Niu, Hongsheng Li, Chang Gong, Li Wang, Fei Liu, Shuya Wang, Yaping Meng, Xianghui Duan, Binghe Xu
Journal: Journal of Clinical Oncology (2024)

1058 Background: Bireociclib is a new selective inhibitor of CDK4/6 which showed promising clinical activity and manageable tolerability both as monotherapy and in combination with endocrine therapy (ET). This phase III study (BRIGHT-2, NCT05077449) was to evaluate the efficacy and safety of Bireociclib plus fulvestrant in HR + /HER2 - advanced breast cancer (ABC) that progressed on or after previous ET. Methods: BRIGHT-2 study was a multicenter, randomized, double-blinded, phase 3 trial in patients with HR + /HER2 - ABC who had progressed on or after prior ET. Eligible patients were randomized 2:1 to receive Bireociclib (360 mg po bid) or placebo with fulvestrant (500 mg im, cycle1 d1, d15, then d1) on each 28-day cycle. The primary endpoint was PFS based on investigator’s assessment per RECIST v1.1. The interim analysis was conducted when 70% PFS events occurred. Results: A total of 305 Chinese female patients were randomly allocated to receive Bireociclib plus fulvestrant (BF, n = 204) or placebo plus fulvestrant (F, n = 101). 208 (68.2%) patients had visceral metastases, 78 (25.6%) patients with primary resistance to ET and 73 (23.9%) patients had received chemotherapy in metastatic setting. As of March 28, 2023, with a median follow-up of 8.7 mo, BF significantly prolonged the PFS per investigator with 12.94 (95%CI, 11.07-NR) mo compared to 7.29 (95%CI, 5.45-11.04) mo in the F group (HR, 0.561; 95%CI, 0.393-0.799; P= 0.0012). The median PFS assessed by blinded independent central review (BICR) were no-reached (95%CI, NR-NR) in BF group and 7.46 (95%CI, 5.49-NR) mo in F group (HR, 0.461; 95%CI, 0.312-0.683; P&lt;0.0001) which were consistent with the investigator’s assessment. The subgroup analyses revealed that in BF group, PFS was improved compared across all subgroups with HRs &lt; 1. For patients with primary resistance to ET, with liver metastases and with bone-only metastases, the HRs were 0.254 (95%CI: 0.128-0.503), 0.381 (95%CI: 0.226-0.644) and 0.234 (95%CI: 0.070-0.787) respectively. In BF group, the most common TEAEs were diarrhea [92.6% (all grades); 5.4% (≥grade 3)], neutropenia [87.3%; 31.4%], leukocytopenia [83.3%; 18.6%] and anemia [66.7%; 10.8%]. Most of AEs were grade 1 or grade 2 and could be alleviated or cured by dose adjustment or symptomatic treatment. Treatment discontinuation due to TEAE was reported in 3 (1.5%) patients with BF. As of March 28, 2023, 120(58.8%) patients in BF were receiving treatment and the trail were ongoing. Conclusions: Bireociclib plus fulvestrant showed superior efficacy for pretreated HR+/HER2- ABC, especially in patients with primary resistance to ET, liver metastases or bone-only metastases. The toxicity of Bireociclib plus fulvestrant were well tolerated and manageable with no new safety signal. Clinical trial information: NCT05077449 .