Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024;20(37):2937-2948.
doi: 10.1080/14796694.2024.2413841. Epub 2024 Oct 21.

Implementing geriatric assessment for dose optimization of CDK4/6 inhibitors in older breast cancer patients

Antonis Valachis  1 , Laura Biganzoli  2 , Athina Christopoulou  3 , Kamilla Fjermeros  4 , Elena Fountzila  5 , Jürgen Geisler  6 , Raquel Gomez-Bravo  7 , Peeter Karihtala  8 , Paris Kosmidis  9 , Angelos Koutras  10 , Helena Linardou  11 , Henrik Lindman  12 , Iván Martínez-Ballestero  13 , Anna Belén Rodríguez  7 , Icro Meattini  14 , Montserrat Munoz-Mateu  7 , Mukhrizah Othman  1 , Amanda Psyrri  15 , Emanuela Risi  2 , Aglaia Schiza  12 , Nikolaos Spathas  11 , Meri Utriainen  8 , Luca Visani  16 , Soledad Ballesteros  17 , Ioannis Basdekis  18 , Susanne Dieroff Hay  19 , Theo Fotis  20 , Samuel Fricker  21 , Gimon de Graaf  22 , Marit Jenset  19 , Tim Kanters  22 , Kostas Lampropoulos  23 , Christiana Markou  24 , Kalliopi Mastoraki  18 , Christina Nanou  25 , José Manuel Reales Aviles  17 , Marianne Santaholma  21 , Thanos Kosmidis  26
Affiliations

Implementing geriatric assessment for dose optimization of CDK4/6 inhibitors in older breast cancer patients

Antonis Valachis et al. Future Oncol. 2024.

Abstract

Current evidence from both randomized trials and real-world studies suggests that older patients with advanced hormone receptor-positive/HER2-negative (HR+/HER2) breast cancer derive clinical benefit from the addition of CDK4/6 inhibitors to endocrine therapy. However, a higher risk for adverse events due to CDK4/6 inhibitors among older patients is evident, leading to a trend of initiating CDK4/6 inhibitors at lower dose in clinical practice, though without evidence. The aim of the IMPORTANT-trial, a pragmatic, multinational, open-label, partly decentralized randomized trial is to investigate whether lower starting dose of CDK4/6 inhibitors combined with endocrine therapy is comparable to full dose in older (≥70 years old) patients with advanced HR+/HER2- breast cancer who are assessed as vulnerable or frail based on comprehensive geriatric assessment.Clinical Trial Registration: NCT06044623 (ClinicalTrials.gov); Registration date: 13 September 2023.

Keywords: CDK4/6 inhibitors; advanced breast cancer; comprehensive geriatric assessment; lower dose; randomized.

Plain language summary

[Box: see text].

PubMed Disclaimer

Conflict of interest statement

A Valachis has received unrestricted research grant from Roche and MSD unrelated to current research project. P Karihtala has been an investigator in studies funded by Lilly, Novartis and Pfizer and has been involved in the advisory boards of Lilly, Novartis and Pfizer. I Meattini declares advisory board participation supported by Eli Lilly, Pfizer, Astra Zeneca, Novartis, Gilead, Menarini StemLine, SeaGen, Daiichi Sankyo. L Biganzoli has received honoraria from Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, SeaGen and unrestricted research grant from Celgene, Genomic Health, Novartis unrelated to current research project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.
IMPORTANT trial overview.
See this image and copyright information in PMC

References

    1. Li J, Huo X, Zhao F, et al. . Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: a systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. doi:10.1001/jamanetworkopen.2020.20312 - DOI - PMC - PubMed
    1. Singh H, Kanapuru B, Smith C, et al. . FDA analysis of enrollment of older adults in clinical trials for cancer drug registration: a 10-year experience by the US Food and Drug Administration. J Clin Oncol. 2017;35(Suppl. 15):e10009. doi:10.1200/JCO.2017.35.15_suppl.10009 - DOI
    1. Howie LJ, Singh H, Bloomquist E, et al. . Outcomes of older women with hormone receptor-positive, human epidermal growth factor receptor-negative metastatic breast cancer treated with a cdk4/6 inhibitor and an aromatase inhibitor: an FDA pooled analysis. J Clin Oncol. 2019;37:3475–3483. doi:10.1200/JCO.18.02217 - DOI - PubMed
    1. Patt D, Liu X, Li B, et al. . Real-world starting dose and outcomes of palbociclib plus an aromatase inhibitor for metastatic breast cancer. J Clin Oncol. 2021;39(Suppl. 15):e13021. doi:10.1200/JCO.2021.39.15_suppl.e13021 - DOI - PubMed
    1. Pulido M, Brain E, Falandry C, et al. . PALOMAGE, a French real-world cohort of elderly women beyond age 70 with advanced breast cancer receiving palbociclib: baseline characteristics and safety evaluation. J Clin Oncol. 2021;39:1012. doi:10.1200/JCO.2021.39.15_suppl.1012 - DOI

Publication types

MeSH terms

Associated data