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The impact of ethnicity on efficacy and toxicity of cyclin D kinase 4/6 inhibitors in advanced breast cancer: a meta-analysis

  • Kirsty Wai Chung Lee
  • Sally Lord
  • Richard S. Finn
  • Elgene Lim
  • Andrew Martin
  • Sherene Loi
  • Jodi Lynch
  • Michael Friedlander
  • Chee Khoon LeeEmail author
Brief Report
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Abstract

Purpose

Adding cyclin-dependent kinase (CDK) 4/6 inhibitor to endocrine therapy improves progression-free survival (PFS) in advanced breast cancer but the impact of ethnicity on efficacy and toxicity is unclear. We aimed to estimate the relative treatment efficacy and toxicity of endocrine therapy with and without CDK4/6 inhibitors, and compare between Asian/non-Asian subgroups.

Method

This meta-analysis included published first-line randomized trials comparing CDK4/6 inhibitor-endocrine therapy versus endocrine monotherapy. Hazard ratios (HR) and 95% confidence intervals (CI) for the overall population and Asian/non-Asian subgroups were extracted. The inverse-variance-weighted method was used to pool treatment estimates of PFS.

Results

Four trials (N = 2499) were included. Patients received combination CDK4/6 inhibitor-endocrine therapy (N = 1441; ribociclib, [46.4%]; palbociclib, [30.8%]; or abemaciclib, [22.8%]) versus endocrine monotherapy (N = 1058). CDK4/6 inhibitor-endocrine therapy was associated with prolonged PFS compared with endocrine monotherapy (HR 0.56; 95% CI 0.50–0.62). In Asians (N = 492), PFS HR was 0.39 (95% CI 0.29–0.51, P < 0.0001). In non-Asians (N = 2007), PFS HR was 0.62 (95% CI 0.54–0.71, P < 0.0001). There was a significant treatment-by-ethnicity interaction (P = 0.002). Toxicity data by ethnic subgroup were only available from two trials (n = 1334) with no convincing evidence that the risk of toxicity between CDK4/6 inhibitor-endocrine therapy and endocrine monotherapy varied by ethnicity.

Conclusion

Adding CDK4/6 inhibitor to endocrine therapy prolongs PFS compared to endocrine therapy alone as first-line treatment in advanced breast cancer. The magnitude of PFS benefit is ethnicity-dependent but there is no interethnic differences in relative treatment-related toxicities. These findings may assist in the design and interpretation of trials, inform economic analyses, and stimulate pharmacogenomic research.

Keywords

Cyclin-dependent kinase 4/6 inhibitor Breast cancer Meta-analysis Ethnicity 

Notes

Acknowledgements

We acknowledge the editorial support provided by Dr Sherilyn Goldstone, PhD (NHMRC Clinical Trials Centre).

Funding

This study did not receive any specific funding.

Compliance with ethical standards

Conflict of interest

RSF acted as a consultant for Astra Zeneca, Bayer, Bristol Myers Squibb, Eisai, Eli Lilly, Novartis, Merck, Pfizer. EL received research funding from Novartis Australia and Bayer (to the institution); acted as a consultant for Novartis Australia, Pfizer Australia, Roche Australia. SL received research funding from Novartis, Bristol Meyers Squibb, Merck, Roche-Genentech, Puma Biotechnology, and Pfizer (to the institution); acted as a consultant for Seattle Genetics, Pfizer, Novartis, BMS, Merck, and Roche-Genentech. MF received remuneration and acted as a consultant for AstraZeneca and MSD. CKL received remuneration and acted as a consultant for AstraZeneca, Roche, Takeda, Boehringer Ingelheim, Novartis. All remaining authors have declared no conflict of interest.

Ethical approval

This research work is a meta-analysis of published data and does not contain any direct involvement of human participants.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kirsty Wai Chung Lee
    • 1
  • Sally Lord
    • 2
  • Richard S. Finn
    • 3
  • Elgene Lim
    • 4
  • Andrew Martin
    • 2
  • Sherene Loi
    • 5
  • Jodi Lynch
    • 1
  • Michael Friedlander
    • 6
  • Chee Khoon Lee
    • 1
    • 2
    Email author
  1. 1.Cancer Care CentreSt George HospitalSydneyAustralia
  2. 2.National Health and Medical Research Council (NHMRC) Clinical Trials CentreUniversity of SydneyCamperdownAustralia
  3. 3.Division of Hematology and Oncology, Department of MedicineDavid Geffen School of Medicine at the University of CaliforniaLos AngelesUSA
  4. 4.Garvan Institute of Medical Research and St Vincent’s Clinical SchoolUniversity of New South WalesSydneyAustralia
  5. 5.Peter MacCallum Cancer CentreMelbourneAustralia
  6. 6.Prince of Wales Hospital, Sydney and Prince of Wales Clinical SchoolUniversity of New South WalesSydneyAustralia

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