CDK4/6 Inhibitor Plus Fulvestrant and Overall Survival in Breast Cancer: FDA Pooled Analysis

By: Emily Rhode
Posted: Monday, March 7, 2022

The addition of a CDK4/6 inhibitor to fulvestrant may improve overall survival for patients with hormone receptor–positive, HER2-negative, advanced or metastatic breast cancer. According to Laleh Amiri-Kordestani, MD, of the U.S. Food and Drug Administration, and colleagues, the results of a pooled analysis were clinically meaningful across various subgroups of patients, regardless of endocrine sensitivity. These findings were published in The Lancet Oncology.

The researchers pooled three phase III randomized trials conducted between 2013 and 2016. The trials included 1,960 patients total; 1,296 patients (66%) were randomly assigned to treatment with a CDK inhibitor plus fulvestrant, and 652 patients (33%) were assigned to treatment with a placebo plus fulvestrant, with 12 patients left untreated. Analysis included pooled populations according to the number of previous lines of systemic endocrine therapy in any disease setting as well as various other clinical subgroups.

Estimated median overall survival favored patients treated with a CDK inhibitor plus fulvestrant by 7.1 months. The estimated hazard ratio for overall survival in all treated patients was 0.77 (95% confidence interval [CI] = 0.68–0.88), with a median follow-up of 43.7 months and deaths in 935 patients (48%).

For patients receiving either treatment combination as first-line systemic endocrine therapy (n = 396), the estimated median overall survival was 7.0 months and again favored patients treated with a CDK inhibitor. The estimated hazard ratio for survival was 0.74 (95% CI = 0.52–1.07). Those who received the combination therapies as second-line or later systemic endocrine therapy (n = 1,552) had an estimated hazard ratio for overall survival of 0.77 (95% CI = 0.67–0.89).

The study authors concluded that “the addition of CDK inhibitors to fulvestrant resulted in a consistent overall survival benefit in all pooled patients and within most clinicopathological subgroups of interest.”

Disclosure: The study authors reported no conflicts of interest.

The Lancet Oncology

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