编者按：超过90%的乳腺癌确诊患者为早期乳腺癌（EBC）患者，尽管有标准的辅助治疗，但大约三分之一的Ⅱ期患者和一半以上的Ⅲ期HR+/HER2-EBC患者都会经历肿瘤复发。NATALEE是一项全球Ⅲ期多中心、随机、开放标签试验，旨在评估瑞波西利联合内分泌治疗（ET）相较于ET辅助治疗HR+/HER2-EBC患者的疗效和安全性。日前，加州大学洛杉矶分校琼森综合癌症中心临床/转化研究主任、肿瘤转化研究（TRIO）主席兼执行董事、NATALEE研究首席研究员Dennis J.Slamon教授在2023年ASCO大会上公布了NATALEE研究结果，肿瘤瞭望特邀采访了Dennis J.Slamon教授，请他分享NATALEE研究最新数据及研究结果。

 

Dennis J.Slamon教授：新的数据显示，HR+早期乳腺癌患者可以通过阻断CDK 4/6通路来使患者实现获益。目前该领域中已经有三种药物获批，其中瑞波西利（ribociclib）和阿贝西利（abemaciclib）这两种药物在早期乳腺癌患者中显示出了显著改善HR+早期乳腺癌患者疗效的前景。

 

Oncology Frontier：Please introduce the current status of diagnosis and treatment of HR+early breast cancer patients.

 

There’s new data emerging that these patients can benefit from blockade of the CDK 4/6 pathway.And there are now three drugs that are approved in this space.In two drugs，ribociclib and abemaciclib are showing promise for improving outcomes for these patients in early breast cancer.

 

Dennis J.Slamon教授：NATALEE研究评估了内分泌治疗联合三种已获批的CDK 4/6抑制剂之一的瑞波西利（ribociclib）在早期乳腺癌患者治疗中的疗效，以观察瑞波西利联合内分泌治疗是否可以减少疾病复发并改善生存率。研究结果表明，与单独使用内分泌治疗相比，瑞波西利联合内分泌治疗可使患者的3年无浸润性疾病生存（iDFS）事件风险降低25.2%（HR=0.748；95%CI：0.618～0.906；P=0.0014）；3年无远处疾病生存（DDFS）事件风险降低26%（HR=0.739；95%CI：0.603～0.905；P=0.0017）。其对总生存的影响目前还在进行中，数据仍不完备。不过随着患者随访的逐渐进行，数据正在慢慢累积。早期结果来看应用前景还是很不错的。

 

△NATALEE试验设计及IDFS和DDFS结果

 

Oncology Frontier：As the principal investigator of the NATALEE trial，would you please introduce the background and related results of the NATALEE trial to us?

 

The background on NATALEE trial was to test one of the three approved CDK 4/6 inhibitors，called ribociclib，in early breast cancer，to see if when combined with hormonal therapy，it can improve outcomes，in other words，decrease relapse and improve survival.Data shows clearly that they can decrease the relapse of the disease by as much as 25%and metastasis by as much as 26%.We are still waiting to see what the impact will be on overall survival.Because the data are still immature with regards to that feature.But the data continue to mature，as we follow up the patients.But the early results are very encouraging.

 

Dennis J.Slamon教授：NATALEE研究结果显示，瑞波西利联合内分泌治疗的早期乳腺癌患者没有出现新发的不良事件。事实上，我们还观察到乳腺癌患者瑞波西利治疗中的不良事件有所减少，可能与NATALEE研究中瑞波西利剂量从600毫克减少到400毫克有关。目前，我们看到瑞波西利显著改善了患者的IDFS和DDFS率，同时我们也在期待总生存期的数据累积完备。该试验的最终目的是实现HR+/HER2-患者的疾病复发率显著降低。

 

△NATALEE研究患者安全性

 

Oncology Frontier：What was the safety profile of patients receiving ribociclib plus endocrine therapy in the NATALEE study?

 

The NATALEE trials show there were no new adverse events from ribociclib.In fact，there was a decrease in the adverse events that we saw in the breast cancer setting.That’s likely due to the fact that we decrease the dose from 600 milligrams to 400 milligrams.Now，knowing that we have seen that it still has this improvement in invasive disease free survival(IDFS)and in metastatic disease，both of which were statistically significant.We are still waiting for maturation of data on overall survival.But the intent is to really decrease the recurrence as that happened in these hormone receptor positive，HER2 negative patients.

 

Dennis J.Slamon教授：该结果的意义在于，从早期数据来看，NATALEE研究可以实现疾病复发率和转移率的降低，这对患者的后续治疗都很重要。生存数据需要进一步跟进，NATALEE研究也明确会对患者进行随访以获取生存数据。今年晚些时候，我们可能将基于500例IDFS事件患者的数据，并对该治疗方案进行最终分析，之后还会有后续的数据进行公布。我们会对患者进行持续随访，直到所有患者完成全部治疗，包括为期5年的内分泌治疗。

 

Oncology Frontier：What is the significance of the positive NATALEE results for patients with HR+breast cancer，and will patients in the NATALEE study be followed for longer periods of time?

 

The significance is that the early data show that we can decrease the recurrence rate and decrease the rate of metastasis，both of which are important.The survival data will require further follow up，and there will absolutely be further followed up on NATALEE.The final analysis for the protocol will be at 500 invasive disease-free survival(IDFS)events that was likely to happen sometime later this year.And then also there will be follow up on a study after that.The patients will continue to be followed until the last patient’s completed all therapy，including their endocrine therapy at 5 years.

 

▌参考文献：

 

1、Pan H，Gray R，Braybrooke J，et al;EBCTCG.20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years.N Engl J Med.2017;377(19):1836-1846.doi:10.1056/NEJMoa1701830

 

2、Iqbal J，Ginsburg O，Rochon PA，Sun P，Narod SA.Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States[published correction appears in JAMA.2015 Jun 9;313(22):2287].JAMA.2015;313(2):165-173.doi:10.1001/jama.2014.17322

 

3、Pan H，Gray R，Braybrooke J，et al;EBCTCG.20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years.N Engl J Med.2017;377(19):1836-1846;(suppl).doi:10.1056/NEJMoa1701830

 

Dennis J.Slamon教授

加州大学洛杉矶分校琼森综合癌症中心临床/转化研究主任

肿瘤转化研究（TRIO）主席兼执行董事

NATALEE研究首席研究员