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FDA Pooled Analysis of CDK4/6 Inhibitor Treatment for Advanced Hormone Receptor–Positive, HER2-Negative Breast Cancer


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In a U.S. Food and Drug Administration (FDA) pooled analysis reported in The Lancet Oncology, Jennifer J. Gao, MD, and colleagues found that the magnitude of progression-free survival benefit with the addition of a cyclin-dependent kinase (CDK) 4/6 inhibitor to endocrine therapy in women with advanced or metastatic hormone receptor–positive, HER2-negative breast cancer was similar across examined subgroups.

Study Details

The analysis included pooled individual patient data from seven phase III randomized breast cancer trials of CDK inhibitors plus endocrine therapy submitted to the FDA before January 1, 2019, in support of marketing applications. In total, 4,200 patients were included: 1,320 received a CDK inhibitor plus an aromatase inhibitor; 932 received an aromatase inhibitor plus placebo; 1,296 received a CDK inhibitor plus fulvestrant; and 652 received fulvestrant plus placebo. Median duration of follow-up was 19.7 months.


“Since the addition of CDK inhibitors to endocrine therapy seemed to benefit all clinicopathological subgroups of interest in this pooled analysis, further research is needed to identify patient subgroups for whom endocrine therapy alone might be appropriate for first-line or second-line treatment of hormone receptor–positive, HER2-negative metastatic breast cancer.”
— Jennifer J. Gao, MD, and colleagues

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Key Findings

Across all seven trials, the difference in estimated median progression-free survival was 8.8 months in favor of treatment with a CDK inhibitor plus endocrine therapy (range across trials = 6.8–13.3 months, hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.54–0.64).

In the first-line aromatase inhibitor setting (n = 2,252), median progression-free survival was 28.0 months in the CDK inhibitor group vs 14.9 months in the placebo group (difference = 13.1 months, HR = 0.55, 95% CI = 0.49–0.62).

In the first-line fulvestrant setting (n = 396), median progression-free survival was not estimable vs 18.6 months (difference = not estimable, HR = 0.58, 95% CI = 0.42–0.80).

In the setting of second- or later-line fulvestrant, the difference in median progression-free survival favoring the CDK inhibitor group vs placebo group was 6.9 months (range across trials = 5.5–7.3 months, HR = 0.56, 95% CI = 0.49–0.64).

The investigators concluded, “Since the addition of CDK inhibitors to endocrine therapy seemed to benefit all clinicopathological subgroups of interest in this pooled analysis, further research is needed to identify patient subgroups for whom endocrine therapy alone might be appropriate for first-line or second-line treatment of hormone receptor–positive, HER2-negative metastatic breast cancer.”

Dr. Gao, of the Center for Drug Evaluation and Research, Office of New Drugs, Office of Oncologic Diseases, U.S. Food and Drug Administration, is the corresponding author for The Lancet Oncology article.

Disclosure: For full disclosures of the study authors, visit www.thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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