As reported in the Journal of Clinical Oncology by Loibl et al, long-term analysis of the German phase II GeparNuevo trial showed continued benefit in outcomes with neoadjuvant durvalumab vs placebo followed by dose-dense epirubicin/cyclophosphamide in patients with triple-negative breast cancer.
Study Details
In the trial, 174 patients were randomly assigned to receive durvalumab (n = 88) or placebo (n = 86) followed by dose-dense chemotherapy. Initial findings at a median follow-up of 43.7 months showed no significant difference in pathologic complete response rate, but significant differences favoring the durvalumab group in 3-year invasive disease–free survival, distant disease–free survival, and overall survival. The current analysis occurred at a median follow-up of 86.4 months.
Key Findings
With additional follow-up, the durvalumab group showed sustained significant improvements vs the placebo group in invasive disease-free survival (hazard ratio [HR] = 0.56, 95% confidence interval [CI] = 0.32–0.99, P = .0431), distant disease–free survival (HR = 0.41, 95% CI = 0.21–0.80, P = .0069), and overall survival (HR = 0.33, 95% CI = 0.14–0.79, P = .0085).
In exploratory analyses, patients with nodal involvement at baseline appeared to derive greater invasive disease–free survival benefit (HR = 0.33, 95% CI = 0.14–0.77; P = .01), with a nominally significant interaction (P interaction = .045) suggesting possible heterogeneity of treatment effect by nodal status. Assessment of stromal tumor–infiltrating lymphocytes (sTILs) in residual disease was performed in 39 evaluable patients among 71 without pathologic complete response; in post hoc analyses, estimated 7-year invasive disease–free survival rates were 92.3% (95% CI = 56.6%–98.9%) in the sTILs-high (> 10%) group vs 51.4% (95% CI = 29.2%–69.7%) in the sTILs-low (≤ 10%) group.
The investigators concluded: “…[A]dding durvalumab to dose-dense [neoadjuvant chemotherapy] without adjuvant continuation of checkpoint inhibition improved long-term survival outcomes, irrespective of the extent of pathologic response. This underscores the necessity to reevaluate the adjuvant continuation of checkpoint inhibition.”
Sibylle Loibl, MD, PhD, of GBG c/o GBG Forschungs GmbH, Neu-Isenburg, Germany, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by AstraZeneca and Celgene (a BMS company). For full disclosures of the study authors, visit ascopubs.org.
