Overall Survival in Patients with HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer Treated with a CDK4/6 Inhibitor plus Fulvestrant: An FDA Pooled Analysis

2021 Year in Review - HER2-Negative Breast Cancer —January 21, 2022


Breast Cancer

Cyclin-dependent kinase (CDK)4/6 inhibitors are oral targeted medicines that are licensed for use in combination with endocrine therapy as a first- or second-line treatment for patients with hormone receptor (HR)-positive, HER2-negative, advanced or metastatic breast cancer.1 CDK4/6 inhibitors with endocrine therapy benefited all clinicopathologic subgroups of patients with HR-positive, HER2-negative, advanced or metastatic breast cancer, so CDK4/6 inhibitors with endocrine therapy appear to help patients whose tumors have varying degrees of endocrine sensitivity.2

Randomized studies of CDK4/6 inhibitors or placebo in combination with fulvestrant in patients with breast cancer submitted to the US Food and Drug Administration before August 1, 2020, were studied.1 All patients studied were aged ≥18 years; had an Eastern Cooperative Oncology Group performance status of 0-1; had advanced or metastatic HR-positive, HER2-negative breast cancer; and had received ≥1 doses of a CDK4/6 inhibitor or placebo in combination with fulvestrant. Patients were looked at as a whole, by the number of previous lines of systemic endocrine therapy used in any illness scenario (first-line or endocrine-naïve vs second-line and later), and by clinicopathologic subgroups of interest. Because of potential patient heterogeneity, the estimated median overall survival was not presented by group when the pooled sample included patients treated across lines of therapy.1

Between 2013 and 2016, 1960 participants were randomly allocated to 1 of 3 pooled trials. Patients were randomly assigned to CDK4/6 inhibitors and 652 (33%) to placebo.1 In all treated patients (N = 1948), the estimated hazard ratio for overall survival was 0.77, with a median follow-up of 43.7 months. Among patients who received CDK4/6 inhibitors or placebo in conjunction with fulvestrant as second-line or later systemic endocrine therapy, the difference in predicted median overall survival favoring CDK4/6 inhibitors was 7.1 months.1

In all pooled patients and throughout most clinicopathologic categories of relevance, adding CDK4/6 inhibitors to fulvestrant resulted in a consistent overall survival advantage.


  1. Gao JJ, Cheng J, Prowell TM, et al. Overall survival in patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer treated with a cyclin-dependent kinase 4/6 inhibitor plus fulvestrant: a US Food and Drug Administration pooled analysis. Lancet Oncol. 2021;22:1573-1581. Erratum in: Lancet Oncol. 2021;22:e472.
  2. Gao JJ, Cheng J, Bloomquist E, et al. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis. Lancet Oncol. 2020;21:250-260.
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Last modified: January 21, 2022

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