Durvalumab in Combination With Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: Long-Term Analysis From the GeparNuevo Trial

Clinical Snapshot

Key Findings

• P Value: iDFS P=0.0431; DDFS P=0.0069; OS P=0.0085

• Effect Size: iDFS HR 0.56, DDFS HR 0.41, OS HR 0.33

• Primary Outcome: Pathologic complete response rate (not reported in abstract)

• Nnt Or Sensitivity: 7-year iDFS rates: 92.3% (high sTILs in RD) vs 51.4% (low sTILs in RD)

• Confidence Interval: iDFS: 95% CI 0.32-0.99; DDFS: 95% CI 0.21-0.80; OS: 95% CI 0.14-0.79

Clinical Application

Requires access to durvalumab and expertise in managing immune checkpoint inhibitors during neoadjuvant treatment Durvalumab available through PBS for other indications; would require TGA approval and PBS listing for this indication. Aligns with current NCCN and ESMO guidelines supporting immunotherapy in TNBC Patients with early triple-negative breast cancer (cT1b-cT4a-d) suitable for neoadjuvant chemotherapy

Abstract

The phase II GeparNuevo trial investigated whether adding durvalumab to neoadjuvant chemotherapy (NACT) only in patients with early triple-negative breast cancer cT1b-cT4a-d would improve pathologic complete response (pCR) rate and patient survival. Hundred and seventy-four patients were randomly assigned to receive durvalumab or placebo concurrently with nab-paclitaxel once per week and followed by dose-dense epirubicin and cyclophosphamide. With 86.4 months of median follow-up compared with the previously reported 43.7 months, durvalumab showed sustained significant improvements in long-term outcomes as defined by STEEP compared with placebo regarding not only invasive disease-free survival (iDFS; hazard ratio [HR], 0.56 [95% CI, 0.32 to 0.99]; stratified log-rank P = .0431), but also distant disease-free survival (DDFS; HR, 0.41 [95% CI, 0.21 to 0.80]; P = .0069) and overall survival (OS; HR, 0.33 [95% CI, 0.14 to 0.79]; P = .0085). All analyses were stratified by stromal tumor-infiltrating lymphocytes (sTILs) at baseline (low [≤10%], intermediate [11%-59%], high [≥60%]). In exploratory subgroup analysis, patients with nodal involvement at baseline demonstrated a greater iDFS benefit (HR, 0.33 [95% CI, 0.144 to 0.771]; P = .01; Pinteraction = 0.045). sTILs in residual disease (RD) could be assessed in 39/71 patients without pCR. Post hoc analyses by sTILs high (>10%) versus low (≤10%) in RD showed estimated 7-year iDFS rates of 92.3% (95% CI, 56.6 to 98.9) and 51.4% (95% CI, 29.2 to 69.7), respectively. Hence, adding durvalumab to dose-dense NACT without adjuvant continuation of checkpoint inhibition improved long-term survival outcomes, irrespective of the extent of pathologic response. This underscores the necessity to re-evaluate the adjuvant continuation of checkpoint inhibition.

References

1. 1.Loibl, S., Untch, M., Huober, J., Schaser, V., Braun, M., Denkert, C., Hartkopf, A., Blohmer, J.-U., Hanusch, C., Link, T., Reinisch, M., Zahm, D.-M., Weide, R., Bjelic-Radisic, V., Staib, P., Tesch, H., Rhiem, K., Lorenz, R., Rey, J., & Schneeweiss, A. (2026). Durvalumab in combination with neoadjuvant chemotherapy in early triple-negative breast cancer: Long-term analysis from the GeparNuevo trial. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-02311