今天，在 #ESMO26 上将展示 NATALEE 的 6 年结果。在此次报告之前，我个人对辅助 CDK4/6 抑制剂带来的生存获益的看法……
NATALEE 中的 6 年 OS 率为 91.86% vs 89.73%：绝对获益为 2.1 个百分点（HR 0.809；95% CI 0.661–0.989；名义单侧 p=0.019）。
monarchE 中 7 年 OS 的绝对获益为 1.8 个百分点（HR 0.842；p=0.027）。我认为，不应将这些获益轻视为“仅 2%”。
在 EBCTCG 分析中，在以蒽环类药物为基础的化疗中加入紫杉烷类药物——这是多年来我们一直认可的标准治疗——带来的 5 年 OS 绝对获益约为 1.9 个百分点。研究人群和随访时间存在差异，因此无法直接比较治疗疗效。然而，我们用来判断几个百分点生存获益的标准应当保持一致。
此外，monarchE 中 95.4% 的患者此前已经接受过化疗。这一生存获益是在化疗和内分泌治疗基础上带来的额外获益。
患者筛选、毒性、治疗时长和成本当然值得讨论。然而，对于经过适当筛选的患者，辅助 CDK4/6 抑制剂的生存获益不应被低估。
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Adjuvant ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): NATALEE 6-y overall survival (OS) and efficacy outcomes
https://esmocongress.esmo.org#ESMO26 | NATALEE – 6-year results (Pre-presentation abstract) 6-year OS: 92.73% vs 89.38% (HR 0.809; nominal p=0.019). iDFS: HR 0.741; absolute benefit of 4.1% at 6 years. In monarchE, a 7-year OS benefit was demonstrated (HR 0.842; p=0.027). NATALEE also shows a promising OS signal; however, formal statistical significance has not yet been established. Looking forward to the presentation....在 X 查看被引用的帖子
- Dr Amol Akhade@SuyogCancer
@dr_yakupergun As expected neither Presenter nor disscusaant touched upon nominal p value 😀 . May be it is too trivial against MAGNITUDE of benifit .
- Bijoy Telivala@BijoyTelivala
@dr_yakupergun @SuyogCancer This 2 % comes at an astronomical financial toxicity
- Dr Amol Akhade@SuyogCancer
@dr_yakupergun Let's wait and see if Presenter or disscusant takes up this point . 🙂👍
- Yakup Ergün@dr_yakupergun
We can wait an hour or two to hear the study authors’ answer, but my personal view is as follows: Absolute benefits in NATALEE become more apparent over time: within the same data cut, the OS difference increases from 1.2 percentage points at 5 years to 2.1 points at 6 years, while the iDFS difference increases from 4.1 to 5.3 points. Breast cancer–specific survival findings also support this pattern. Given that recurrences and subsequent deaths in HR-positive disease extend over many years, early OS differences should not be viewed as the limit of a treatment’s overall contribution. The statistical distinction needs to be clear. OS is a secondary endpoint in NATALEE, and a confirmatory testing strategy controlling the overall type I error across multiple endpoints and repeated OS analyses was not prespecified. In monarchE, OS was assessed against a prespecified significance boundary accounting for repeated analyses. I wish NATALEE had included a similar framework for OS. However, saying “the p value is nominal, therefore the OS result is not significant” is also an oversimplification. The 6-year OS analysis shows nominal statistical significance: HR 0.809; 95% CI 0.661–0.989; one-sided nominal p=0.019. This does not carry the same evidentiary weight as a multiplicity-adjusted, confirmatory OS result, but it does not invalidate the observed survival difference either. The emergence of an OS benefit with longer follow-up in monarchE illustrates why time matters in this disease. I consider a 2.1-percentage-point absolute OS benefit at 6 years clinically meaningful in this study population. Although there is no head-to-head comparison, I believe abemaciclib and ribociclib may provide long-term benefits of a similar magnitude in appropriately selected populations. This is my interpretation of the available evidence, rather than a demonstrated equivalence. We can certainly discuss NNT, censoring, numbers at risk, uncertainty around the estimates, toxicity, and treatment burden. But if we reduce our assessment to whether a p value crosses a threshold, we risk overlooking clinically valuable gains—particularly in HR-positive breast cancer. Sorry, this turned into quite a long comment, almost like a letter. I just wanted to go into a bit more detail🙏
- Dr Amol Akhade@SuyogCancer
@dr_yakupergun Is this OS statistically significant? 🤔
来源：Yakup Ergün · x.com