Addition of Carboplatin to Sequential Taxane-Anthracycline Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer: A Phase III Randomized Controlled Trial.

Methods

In this phase III trial, patients with TNBC were randomly assigned, after stratification by stage and menopausal status, to receive neoadjuvant chemotherapy comprising once-per-week carboplatin (AUC-2) plus paclitaxel (100 mg/m2) for 8 weeks, followed by four cycles of anthracycline plus cyclophosphamide, or same chemotherapy without carboplatin.

在这项III期试验中，经过按阶段和绝经状态分层后，将TNBC患者随机分配，接受每周一次卡铂（AUC-2）加紫杉醇（100 mg/m2）的新辅助化疗8周，随后进行四周期的蒽环类加环磷酰胺化疗，或相同化疗方案但不加卡铂。

The primary end point was event-free survival (EFS), and secondary end points were overall survival(OS) and pathologic complete response.

主要终点事件是无事件生存（EFS），次要终点事件是总生存（OS）和病理完全缓解。

This is the prespecified primary analysis of this study.

这是本研究预先设定的主要分析。

Results

Of 720 patients randomly assigned between April 2010 and January 2020, 717 (platinum 361, control 356) were included in modified intention-to-treatanalysis.

在2010年4月至2020年1月间随机分配的720名患者中，有717名（铂类361名，对照组356名）被纳入改良意向治疗分析。

At median follow-up of 67.6 months, in platinum and control arms, there were 111/361 and 131/356 EFS events (hazard ratio[HR], 0.80 [95% CI, 0.62 to 1.03]; two-sided unstratified P = .081), with 5-year EFS of 70.7% (95% CI, 65.8% to 75.6%) and 64.1% (95% CI, 59.0% to 69.2%), respectively, and 94/361 and 121/356 deaths (HR, 0.74 [95% CI, 0.57 to 0.97]; nominal P = .029), with 5-year OS of 74.4% and 66.8%, respectively.

在中位随访67.6个月时，铂类组和对照组分别有111/361和131/356的无事件生存（EFS）事件（风险比[HR]，0.80 [95%置信区间，0.62至1.03]；双侧非分层P = .081），5年EFS分别为70.7%（95%置信区间，65.8%至75.6%）和64.1%（95%置信区间，59.0%至69.2%），以及94/361和121/356的死亡（HR，0.74 [95%置信区间，0.57至0.97]；名义P = .029），5年总生存（OS）分别为74.4%和66.8%。

In premenopausal patients, EFS (HR, 0.61 [95% CI, 0.43 to 0.84]; nominal P = .003; 5-year EFS 75.0% v 59.6%) and OS (HR, 0.57 [95% CI, 0.40 to 0.82]; nominal P = .002; 5-year OS 78.2% v 64.6%) were significantly higher, while in postmenopausal patients, EFS (HR, 1.19 [95% CI, 0.80 to 1.78]; nominal P = .386) and OS (HR, 1.06 [95% CI, 0.70 to 1.61]; nominal P = .772) were not significantly different, in platinum versus control arm.

在绝经前患者中，无进展生存期（EFS）（风险比[HR]，0.61 [95% 置信区间，0.43至0.84]；名义P值= .003；5年EFS为75.0%对比59.6%）和总生存期（OS）（HR，0.57 [95% CI, 0.40至0.82]；名义P值= .002；5年OS为78.2%对比64.6%）显著更高，而在绝经后患者中，EFS（HR，1.19 [95% CI, 0.80至1.78]；名义P值= .386）和OS（HR，1.06 [95% CI, 0.70至1.61]；名义P值= .772）在铂类药物与对照组之间没有显著差异。

There was statistically significant interaction between study intervention and menopausal status for EFS and OS, with a benefit of adding platinum in premenopausal but not in postmenopausal patients.

研究干预与绝经状态之间对于EFS和OS存在统计学上显著的相互作用，对于绝经前患者添加铂类药物有益，而对于绝经后患者则没有。

There was more grade ≥3 myelosuppression in carboplatin arm, but there was no difference in nonhematologic toxicities.

卡铂组中3级或更高级别的骨髓抑制发生率更高，但非血液学毒性没有差异。

Conclusions

Carboplatin did not significantly increase EFS but significantly increased the OS in patients with TNBC, with benefits confined to premenopausal patients.

卡铂并未显著提高无进展生存期，但显著提高了三阴性乳腺癌患者的总生存期，且益处仅限于绝经前患者。