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Evidence summaries

Cyclin-Dependent Kinase Inhibitor for Advanced Breast Cancer

The addition of cyclin-dependent kinase inhibitor (CDKi) to endocrine therapy appears to reduce mortality and increase progressive-free survival in hormone receptor-positive, HER2-negative, advanced breast cancer compared with endocrine therapy alone. Level of evidence: "B"

The certainty of the evidence is downgraded by study quality (phase three trials only).

Summary

A pooled analysis 1 included individual patient data from 3 phase 3 randomised trials of cyclin-dependent kinase inhibitor (CDKi) or placebo in combination with fulvestrant in patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer (n=1960). The estimated HR for overall survival was 0.77 (95% CI 0.68 to 0.88), with a median follow-up of 43.7 months and deaths in 935 (48%) patients. The difference in estimated median overall survival was 7.1 months, favouring CDKi. In patients who received CDKi or placebo in combination with fulvestrant as second-line or later systemic endocrine therapy (3 trials; n=1552), the estimated HR for overall survival was 0.77 (95% CI 0.67 to 0.89), with a median follow-up of 45.1 months (95% CI 39.2 to 48.5). 812 (52%) of these patients died. The difference in estimated median overall survival was 7.0 months, favouring CDKi.

Another analysis 2 included individual patient data from 7 phase 3 RCTs (n=4200) of CDKi plus endocrine therapy (an aromatase inhibitor letrozole or anastrazole, or antioestrogen fulvestrant). The difference in estimated median progression-free survival (PFS) was 8.8 months in favour of CDKi plus endocrine therapy over placebo plus endocrine therapy (range 6.8 to 13.3 months; HR 0.59, 95% CI 0.54 to 0.64). In first-line aromatase inhibitor-treated patients (n=2252), the difference in PFS in the CDKi plus aromatase inhibitor group versus placebo plus aromatase inhibitor group was 13.1 months (range 13.0 to 13.3 months; HR 0.55, 95% CI 0.49 to 0.62). In the second-line setting and beyond (n=1552), the difference in PFS between the CDKi plus fulvestrant group and the placebo plus fulvestrant group was 6.9 months in favour of the CDKi (range 5.5 to 7.3 months; HR 0.56, 95% CI 0.49 to 0.64).

Clinical comments

Note

Date of latest search:2022-01-03

    References

    • 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 USFood and Drug Administration pooled analysis. Lancet Oncol 2021;22(11):1573-1581. [PubMed]
    • 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(2):250-260. [PubMed]

Primary/Secondary Keywords