Editor’s Note: At the 2025 ESMO Annual Congress, the long-term follow-up results of the GeparNuevo trial (Abstract #292MO) were presented. The data showed that although durvalumab combined with neoadjuvant chemotherapy did not significantly improve the pathological complete response (pCR) rate, it significantly prolonged survival outcomes, including invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS). Notably, among patients who achieved pCR, the 7-year OS rate reached 100% in the durvalumab group, suggesting that immunotherapy may provide long-term benefits through sustained immune surveillance. Oncology Frontier invited Professor Zhang Juliang from Xijing Hospital, Air Force Medical University, to comment on these findings and discuss strategies for optimizing immunotherapy in early triple-negative breast cancer (TNBC). Study Overview
Title: Durvalumab in combination with neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC): Long-term analysis from the GeparNuevo trial
Background
The phase II GeparNuevo trial evaluated the benefit of adding the immune checkpoint inhibitor durvalumab to neoadjuvant chemotherapy in early TNBC. While durvalumab did not significantly increase the primary endpoint—pCR rate—it demonstrated significant improvements in key secondary endpoints, including iDFS, DDFS, and OS, compared with placebo. The 2025 presentation reported the updated long-term survival outcomes.
Methods
The trial enrolled patients with pathologically confirmed early TNBC (cT1b–cT4a-d), who were randomized 1:1 to receive:
- Durvalumab + neoadjuvant chemotherapy (nab-paclitaxel followed by dose-dense EC), or
- Placebo + the same chemotherapy regimen.
Durvalumab was administered only during the neoadjuvant phase, with no post-surgical adjuvant use. Patients were stratified by stromal tumor-infiltrating lymphocytes (sTILs) levels:
- High sTILs: >10%
- Low sTILs: <10%
Results
Between June 2016 and September 2017, 174 patients were enrolled. After a median follow-up of 86.4 months (range: 4.9–103), 50 iDFS events occurred.
- 6-year iDFS: 79.6% (durvalumab) vs. 62.8% (placebo)
- 7-year iDFS: 73.7% (durvalumab) vs. 60.7% (placebo)
Durvalumab demonstrated sustained iDFS benefits, along with significant improvements in DDFS and OS.
Among patients achieving pCR, the 7-year OS rate was 100% in the durvalumab group, compared to 82.5% in the placebo group (P = 0.0053).
In the 71 non-pCR patients, 39 had evaluable residual disease (RD) for sTIL analysis:
- High sTILs (>10%): 7-year iDFS = 92.3% (56.6%–98.9%)
- Low sTILs (<10%): 7-year iDFS = 51.4% (29.2%–69.7%)
An exploratory subgroup analysis suggested that patients with initially node-positive disease derived greater benefit from durvalumab in iDFS (HR 0.33; 95% CI: 0.144–0.771; P = 0.01; interaction P = 0.045).
Conclusion
Even when used only during the neoadjuvant phase, durvalumab significantly improved long-term survival outcomes in early TNBC. These benefits were especially pronounced among patients who achieved pCR, reinforcing the potential role of immune checkpoint inhibitors in early disease management.
The findings also raise important questions about the need for adjuvant immunotherapy—suggesting that neoadjuvant immune activation alone may yield durable survival advantages.
Expert Commentary — Professor Zhang Juliang
Immune checkpoint inhibitors (ICIs) have become an integral part of neoadjuvant therapy for early TNBC, a strategy now supported by international guidelines, including the NCCN. However, several key questions remain—such as optimal treatment duration and whether patients who achieve pCR from chemotherapy alone truly need additional immunotherapy.
The long-term results from GeparNuevo provide valuable insight. Although durvalumab did not significantly raise pCR rates, it led to remarkable improvements in long-term survival outcomes—iDFS, DDFS, and OS. Even among patients who achieved pCR, the survival advantage remained statistically significant.
This indicates that not all pCRs are equivalent—and that ICIs may exert long-lasting effects by maintaining immune activation and surveillance, enabling the immune system to eradicate micrometastatic disease that persists even after chemotherapy-induced remission.
The duration of immunotherapy remains another critical area for investigation. If neoadjuvant immunotherapy effectively “re-educates” the immune system to recognize and eliminate tumor cells, continued adjuvant immunotherapy may not always be necessary. This could explain why trials such as IMpassion030, which tested adjuvant ICI use, did not show significant benefits—highlighting the need for further exploration into timing and duration of immune checkpoint therapy.
Professor Zhang Juliang Department of Breast, Thyroid, and Vascular Surgery Xijing Hospital, Air Force Medical University
