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Rishabh Jain: ctDNA Flips the Script – Who Needs Early CDK4/6i in HR+/HER2- ABC?

Rishabh Jain/X

Sep 8, 2025, 15:51

Rishabh Jain: ctDNA Flips the Script – Who Needs Early CDK4/6i in HR+/HER2- ABC?

Rishabh Jain, Medical Oncologist at AIIMS, shared a post on X about a paper by Elisabeth M. Jongbloed et al. published in Nature Medicine:

“ctDNA flips the script: Who needs early CDK4/6i in HR+/HER2- ABC?

SONIA translational analysis (n=409; randomized phase III) | Nature Medicine 2025

Arms

1L AI + CDK4/6i – Fulvestrant
1L AI – Fulvestrant + CDK4/6i

Key results (by baseline ctDNA aneuploidy score)

High ctDNA (≥5) – clear benefit from 1L CDK4/6i

PFS1 HR 0.40 (95% CI 0.27–0.60)

PFS2 HR 0.58 (95% CI 0.38–0.88)

Low ctDNA (<5) – trend favoring 2L CDK4/6i

PFS2 HR 1.36 (95% CI 0.95–1.96)

Context

1L CDK4/6i = high toxicity and high cost
ctDNA can guide escalation vs de-escalation

Takeaway

Pretreatment ctDNA (mFast-SeqS) identifies who truly benefits from upfront CDK4/6i – a step towards biomarker-driven sequencing in HR+/HER2– MBC.

Full paper
Jongbloed EM et al. Nature Medicine 2025.”

Title: Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer: circulating tumor DNA analysis of a randomized phase 3 trial

Authors: Elisabeth M. Jongbloed, Noor Wortelboer, Vanja de Weerd, Corine M. Beaufort, Kirsten Ruigrok-Ritstier, Mai N. Van, Jaco Kraan, Annette A. van Zweeden, Annemieke van der Padt-Pruijsten, Lisanne C. Hamming, Inge R. Konings, Gabe S. Sonke, Esther Oomen-de Hoop, John W. M. Martens, Agnes Jager, Saskia M. Wilting

You can read the Full Article in Nature Medicine.

Rishabh Jain: ctDNA Flips the Script - Who Needs Early CDK4/6i in HR+/HER2- ABC?

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Rishabh Jain: ctDNA Flips the Script – Who Needs Early CDK4/6i in HR+/HER2- ABC?

“ctDNA flips the script: Who needs early CDK4/6i in HR+/HER2- ABC?