The addition of bireociclib to fulvestrant significantly improved progression-free survival (PFS) in patients with advanced breast cancer who progressed after endocrine therapy (ET), with improvements shown across subgroups by menopausal status, metastatic sites, prior treatment, disease-free interval, and ESR1/PIK3CA/TP53 alterations, according to the results of a phase 3 trial published in JAMA Oncology.

In the BRIGHT-2 clinical study, researchers in China randomly assigned patients to 360 mg bireociclib, a novel CDK4/6 inhibitor + fulvestrant, or placebo + fulvestrant, administered orally once every 12 hours. Fulvestrant was administered intramuscularly at 500 mg on days 1 and 15 of the initial 28-day cycle, then on day 1 of each subsequent cycle.

Previously reported interim data showed that bireociclib + fulvestrant improved PFS in this patient population compared with placebo. The researchers also observed a favorable safety profile associated with bireociclib, including a low rate of treatment discontinuation due to adverse events.

The final analysis included data from 305 patients with 204 patients assigned to bireociclib and 101 patients assigned to placebo. The median follow-up was 19 months.

The study met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement to PFS for patients assigned to bireociclib + fulvestrant. Assignment to bireociclib was further associated with superior objective response.

Data on overall survival, a key secondary endpoint, were not mature at the time of reporting because median overall survival was not reached in either group. Patients assigned to bireociclib had numerically higher overall survival rates than those assigned to placebo at 12 months, 15 months, and 18 months.

Safety data were consistent with previously reported outcomes and with the known safety profiles of CDK4/6 inhibitors. Most adverse events associated with bireociclib were low grade and were managed through treatment or dose interruptions.

Treatment-related adverse events leading to death occurred in seven patients assigned to bireociclib, with one sudden cardiac death and two cases of infectious pneumonia deemed related to adverse events.

The researchers noted that treatment with bireociclib was favored in all subgroup analyses, including menopausal status, previous treatment, disease-free interval, and genomic alterations. They further noted that patients who experienced early-onset diarrhea derived greater benefit from treatment with bireociclib.

Study limitations included the post hoc nature of the genomic analyses, which relied on previously collected circulating tumor DNA, and the exclusive recruitment of Chinese patients, which may limit global application of the study’s findings.

“The findings of this randomized clinical trial provide valuable evidence on the efficacy and safety of bireociclib plus fulvestrant in patients with HR+, [HER2-] advanced breast cancer in Chinese clinical practice and supports the potential for individualized strategies in specific subgroups.”

- Jiayu Wang, MD, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and colleagues wrote.

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By Cameron Kelsall

References:

https://jamanetwork.com/journals/jamaoncology/article-abstract/2846699

https://clinicaltrials.gov/study/NCT05077449

Disclosures: Some authors declared financial ties to drugmakers. See full study for details. Xuanzhu Biopharmaceutical Co., Ltd., supported the study.

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