CDK4/6 inhibitors + fulvestrant improve OS in HR-positive, HER2-negative advanced breast cancer

The addition of a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor to fulvestrant provides a consistent benefit in overall survival (OS) in patients with hormone receptor (HR)–positive, HER2-negative, advanced or metastatic breast cancer in first-, second- and later-line settings and in most clinicopathological subgroups of interest, results of a US FDA pooled analysis of have shown.

The exploratory analysis included data from 1,960 adult patients with HR-positive, HER2-negative, advanced or metastatic breast cancer and an Eastern Cooperative Oncology group performance status of 0–1 enrolled in three randomized phase III trials of CDK 4/6 inhibitors.  The data were submitted to the US FDA and approved before 1 August 2020 in support of marketing applications. [Lancet Oncol 2021;doi:10.1016/S1470-2045(21)00472-1]

In the trials, 1,296 patients (66 percent) received a CDK 4/6 inhibitor in combination with fulvestrant, 652 patients (33 percent) received placebo plus fulvestrant, while 12 patients were not treated.

In all treated patients (n=1,948), the addition of a CDK 4/6 inhibitor to fulvestrant was found to provide an estimated 23 percent improvement in OS vs placebo plus fulvestrant (estimated hazard ratio, 0.77; 95 percent confidence interval [CI], 0.69 to 0.88) over a median follow-up of 43.7 months. The improvement in estimated median OS was 7.1 months with CDK 4/6 inhibitors vs placebo.

Among patients who received a CDK 4/6 inhibitor or placebo plus fulvestrant as first-line endocrine therapy (two trials; n=396), the improvement in OS was 26 percent (hazard ratio, 0.74; 95 percent CI, 0.52 to 1.07) over a median follow-up of 39.4 months. Median OS was not estimable in the CDK 4/6 inhibitor group, compared with 45.7 months in the placebo group.

In patients treated in second- or later-line endocrine therapy settings (three trials; n=1,552), the addition of a CDK 4/6 inhibitor to fulvestrant provided a 23 percent improvement in OS vs placebo plus fulvestrant (estimated hazard ratio, 0.77; 95 percent CI, 0.67 to 0.89) over a median follow-up of 45.1 months. The improvement in estimated median OS was 7.0 months with CDK 4/6 inhibitors vs placebo.

“The addition of CDK 4/6 inhibitors to fulvestrant resulted in a consistent OS benefit in all pooled patients and within most clinicopathological subgroups of interest. These findings support the existing standard of care of CDK 4/6 inhibitors plus fulvestrant for treatment of patients with HR-positive, HER2-negative advanced breast cancer,” the investigators concluded.