Is Shortening TNBC Treatment Safe? The Neo-n Trial and SABCS 2025 ctDNA Findings
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Neoadjuvant Immunotherapy in Early-Stage Triple-Negative Breast Cancer: SABCS 2025 Findings from the Neo-n Trial
Triple-negative breast cancer (TNBC) is a challenging subtype known for its aggressive nature and risk of early recurrence. Although adding immunotherapy to standard chemotherapy increases pCR, the questions ‘Is a short course of treatment enough?’ and ‘Can we predict recurrence?’ remain open. Neo-n demonstrated the efficacy of the Nivolumab combination and the power of ctDNAto predict recurrence at SABCS 2025.
1) What is the aim of the Neo-n trial?
Led by Sherene Loi, this study (NCT04073457) is testing, in operable early-stage TNBC (Stage I–III), a shorter immuno-oncology (IO) approach in place of standard prolonged regimens. It also focuses on the ability of circulating tumor DNA (ctDNA) in the blood to detect residual disease (MRD) and predict recurrence. [1]
2) Design: Two different approaches
A total of 74 patients were treated using two different strategies:
• Lead-in cohort (n=20): Nivolumab loading first, followed by chemotherapy.
• Concurrent cohort (n=54): Concurrent Nivolumab + Carboplatin/Paclitaxel from the outset.
In both groups, the neoadjuvant phase lasted only 9 weeks and was followed by adjuvant Nivolumab after surgery.
3) Primary Outcome: Success in 3-Year EFS
Event-free survival (%)What the data mean
Compared with historical EFS rates in the 70–80% range, the 92.4% success rate in the lead-in cohort is particularly striking. This indicates the potential value of ‘priming’ the immune system with immunotherapy in advance.
4) Summary of Key Findings
| Parameter | Result | Detail |
|---|---|---|
| pCR (Complete Response) | 58% - 65% | Numerically higher in the lead-in group (65%). |
| ctDNA Clearance | Fell to 18% | A decline from 91% positivity at baseline to 18% with treatment. |
| Prediction of Recurrence | HR 4.2 | Recurrence risk was 4 times higher in those who remained ctDNA-positive. |
| Overall Survival | HR 0.65 | The trend is favorable, but the data are not yet mature. |
Note: ctDNA analysis was performed using ultrasensitive NGS (Next-Generation Sequencing).
5) A Game Changer: ctDNA Dynamics
The most striking aspect of the study is that circulating tumor DNA (ctDNA) in the blood acts like a ‘molecular oracle’ . ctDNA clearance predicted 3-year EFS with 90% accuracy . In other words, 90% of patients whose blood became free of tumor DNA did not experience recurrence.
Safety Profile
The addition of Nivolumab showed a manageable toxicity profile. Grade 3+ adverse events occurred in 40%, while immune-related adverse events (thyroiditis, pneumonitis, etc.) remained around 10%.
Rates of dose interruption (15%) and treatment discontinuation (5%) were acceptable compared with longer regimens such as KEYNOTE-522. ctDNA monitoring caused no additional adverse effects.
5 Frequently Asked Questions
Expert Commentary
Neo-n strengthens hopes of ‘achieving the same success with less toxicity’ (de-escalation) in TNBC treatment. In particular, using ctDNA as a Minimal Residual Disease (MRD) marker may be the key that enables us to decide in the future ‘who needs additional treatment and who does not’.
References
- Loi S, et al. Neo-n (neon): three-year event-free survival and ultrasensitive ctDNA dynamics... Cancer Res. 2025;85(suppl 9):PD7-10. ↩︎
- SABCS 2025 Poster Spotlight 7: Lead-in EFS 92.4%, ctDNA predictive value 90%. ↩︎
Disclaimer: This content is not medical advice; treatment decisions should be made under the guidance of an oncology specialist.
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