Neoadjuvant Paclitaxel/Olaparib in Comparison to Paclitaxel/Carboplatin in Patients with HER2-Negative Breast Cancer and HRD-Long-term Survival of the GeparOLA Study.

HRD was defined by high HRD score or germline (g)/tumor (t) BRCA1/2 mutations (g/tBRCA1/2mut).

HRD 的定义是基于高 HRD 评分或携带遗传性（g）/肿瘤（t）BRCA1/2 突变（g/tBRCA1/2mut）。

In this study, we report long-term outcome data.

在本研究中，我们报告了长期结果数据。

patients_and_methods

GeparOLA (NCT02789332) was a randomized, multicenter, prospective, open-label, phase II trial. Patients with HER2-negative early breast cancer with HRD with an indication for chemotherapy (cT2-cT4a-d or cT1c and cN+ or cT1c and pNSLN+ or cT1c and triple-negative breast cancer, or cT1c and Ki-67 >20%) were randomly assigned to PO or paclitaxel + carboplatin (PCb), both followed by epirubicin + cyclophosphamide.

GeparOLA (NCT02789332) 是一项随机、多中心、前瞻性、开放标签的II期临床试验。

Long-term efficacy endpoints were secondary endpoints and included invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival, with a planned median follow-up of >4 years.

长期疗效终点是次要终点，包括侵袭性疾病无复发生存期（iDFS）、远处疾病无复发生存期（DDFS）和总生存期，计划的中位随访时间超过4年。

Results

Between September 2016 and July 2018, 107 patients were randomized and 106 (PO N = 69 and PCb N = 37) started treatment.

在2016年9月至2018年7月期间，共有107名患者被随机分配，其中106名（PO组N=69，PCb组N=37）开始接受治疗。

The median age was 47.0 years; of all patients, 35.8% had cT1 tumors, 31.4% were cN+, 86.8% had G3 tumors, 89.6% had Ki-67 >20%, and 72.6% were triple negative.

中位年龄为47.0岁；所有患者中，35.8%有cT1肿瘤，31.4%为cN+，86.8%有G3肿瘤，89.6%的Ki-67>20%，72.6%为三阴性。

After a median follow-up of 49.8 months, 18 (15 in PO and three in PCb) iDFS events and seven (six in PO and one in PCb) deaths were reported.

中位随访时间为49.8个月，报告了18例（15例在PO，3例在PCb）iDFS事件和7例（6例在PO，1例在PCb）死亡。

The 4-year iDFS (76.0% PO vs. 88.5% PCb, hazard ratio= 2.86; 95% CI, 0.83-9.90; log-rank P = 0.081), DDFS (81.2% PO vs. 93.4% PCb, hazard ratio= 3.03; 95% CI, 0.67-13.67; log-rank P = 0.129), and overall survival(89.2% PO vs. 96.9% PCb, hazard ratio= 3.27; 95% CI, 0.39-27.20; log-rank P = 0.244) tended to be inferior with olaparib.

4年无病生存率（76.0% PO vs. 88.5% PCb, 风险比=2.86; 95% 置信区间, 0.83-9.90; log-rank P = 0.081）、无远处转移生存率（81.2% PO vs. 93.4% PCb, 风险比=3.03; 95% 置信区间, 0.67-13.67; log-rank P = 0.129）和总生存（89.2% PO vs. 96.9% PCb, 风险比=3.27; 95% 置信区间, 0.39-27.20; log-rank P = 0.244）在使用奥拉帕利治疗的患者中倾向于较差。

Patients without g/tBRCA1/2mut benefited from Cb (seven of 30 patients had iDFS/DDFS events in PO vs. 0/16 in PCb; log-rank P = 0.037), whereas no difference for patients with g/tBRCA1/2mut was observed (hazard ratio= 1.16, log-rank P = 0.83).

没有g/tBRCA1/2突变的患者从Cb治疗中受益（30名患者中有7名在PO组发生iDFS/DDFS事件，而在PCb组为0/16；log-rank P = 0.037），而对于有g/tBRCA1/2突变的患者则没有观察到差异（风险比=1.16, log-rank P = 0.83）。

Conclusions

For HER2-negative early breast cancer with HRD, olaparib showed a tendency for inferior outcomes compared with Cb, particularly in patients without g/tBRCA1/2mut.

对于HER2阴性的早期乳腺癌伴有同源重组缺陷（HRD），奥拉帕利显示出与卡铂（Cb）相比结果较差的趋势，特别是在没有g/tBRCA1/2突变的患者中。

In patients with g/tBRCA1/2mut, olaparib may replace Cb.

在g/tBRCA1/2突变的患者中，奥拉帕利可能会取代卡铂（Cb）。