German Breast Group, Neu-Isenburg, Germany; Center for Hematology and Oncology Bethanien, Frankfurt, Germany.
National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany.
Ann Oncol. 2022 Nov;33(11):1149-1158. doi: 10.1016/j.annonc.2022.07.1940. Epub 2022 Aug 9.
Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287).
Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS).
A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred.
Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.
在早期乳腺癌中，将免疫检查点抑制剂加入新辅助化疗（NACT）是一种很有前途的策略，但目前尚不清楚最佳治疗持续时间。在 GeparNuevo（NCT02685059）试验中，先前报道的将 durvalumab 加入 NACT 可使病理完全缓解（pCR）率适度增加 9%（P=0.287）。
cT1b-cT4a-d 三阴性乳腺癌（TNBC）患者接受 durvalumab 1.5 g 或安慰剂，每 4 周一次，与每周一次的 nab-paclitaxel 125 mg/m 联合使用 12 周，随后每 4 周一次 durvalumab/安慰剂联合表柔比星/环磷酰胺每 2 周一次，随后进行手术。手术后不再继续使用 durvalumab。主要终点是 pCR。次要终点包括浸润性无病生存期（iDFS）、远处无病生存期（DDFS）和总生存期（OS）。
共有 174 例患者于 2016 年 6 月至 2017 年 10 月之间随机分组。中位随访 43.7 个月后，34 例患者出现了疾病进展。尽管 pCR 率的增加无统计学意义，但在 3 年 iDFS、DDFS 和 OS 方面观察到了显著差异：durvalumab 组的 3 年 iDFS 为 85.6%，安慰剂组为 77.2%[风险比（HR）0.48，95%置信区间（CI）0.24-0.97，分层对数秩检验 P=0.036]；DDFS 为 91.7%和 78.4%（HR 0.31，95%CI 0.13-0.74，P=0.005）；OS 为 95.2%和 83.5%（HR 0.24，95%CI 0.08-0.72，P=0.006）。接受 durvalumab 的 pCR 患者 3 年 iDFS 为 95.5%，无 pCR 患者为 86.1%（HR 0.22，95%CI 0.05-1.06）。在非 pCR 队列中，3 年 iDFS 为 76.3%和 69.7%（HR 0.67，95%CI 0.29-1.54）。多变量分析证实 durvalumab 的效果独立于 pCR 效果。未出现新的安全信号。
在 TNBC 中，durvalumab 加入 NACT 可显著改善生存，尽管 pCR 略有增加且没有辅助 durvalumab 成分。需要进一步研究以阐明早期 TNBC 治疗中检查点抑制剂的最佳持续时间和顺序。
