Merck (known as MSD outside of the United States and Canada), announced the first-time presentation of overall survival (OS) results from the Phase III KEYNOTE-522 trial evaluating Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with chemotherapy as pre-operative (neoadjuvant) treatment and then continuing as a single agent after surgery (adjuvant) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC).

默克公司（在美国和加拿大以外被称为MSD）宣布首次介绍了III期KEYNOTE-522试验的总生存期（OS）结果，该试验评估了默克公司的抗PD-1疗法Keytruda（pembrolizumab），联合化疗作为术前（新辅助）治疗，然后在手术（辅助）后继续作为单一药物治疗高危早期三阴性乳腺癌（TNBC）患者。

After a median follow-up of 75.1 months (range, 65.9-84.0), the Keytruda regimen significantly improved OS, a key secondary endpoint, reducing the risk of death by 34% (HR=0.66 [95% CI, 0.50-0.87]; p=0.0015) in patients with high-risk early-stage TNBC compared to the chemotherapy-placebo regimen (placebo plus chemotherapy followed by placebo after surgery).

在中位随访75.1个月（范围65.9-84.0）后，Keytruda方案显着改善了OS，这是一个关键的次要终点，将高危早期TNBC患者的死亡风险降低了34%（HR=0.66[95%CI，0.50-0.87]；p=0.0015）与化疗安慰剂方案（安慰剂加化疗，术后服用安慰剂）相比。

The five-year OS rate was 86.6% (95% CI, 84.0-88.8) for patients who received the Keytruda regimen versus 81.7% (95% CI, 77.5-85.2) for patients who received the chemotherapy-placebo regimen. Median OS was not reached in either group. The safety profile of Keytruda was consistent with that observed in previously reported studies with no new safety signals observed..

接受Keytruda方案的患者的五年OS率为86.6%（95%CI，84.0-88.8），而接受化疗安慰剂方案的患者的五年OS率为81.7%（95%CI，77.5-85.2）。两组均未达到中位OS。Keytruda的安全性与先前报道的研究中观察到的一致，没有观察到新的安全信号。。

These late-breaking data are being presented for the first time  during a Presidential Symposium session at the European Society for Medical Oncology (ESMO) Congress 2024 (presentation #LBA4) and were selected for an official Press Briefing. These data are also being simultaneously published in the New England Journal of Medicine .

这些最新的数据首次在2024年欧洲肿瘤内科学会（ESMO）大会（演示文稿#LBA4）的总统研讨会上提交，并被选为官方新闻发布会。这些数据也同时发表在《新英格兰医学杂志》上。

Keytruda is the first and only immunotherapy-based regimen to show a statistically significant and clinically meaningful improvement in OS as neoadjuvant treatment with chemotherapy and then continued as a single agent as adjuvant treatment compared to placebo plus chemotherapy followed by placebo after surgery in patients with high-risk early-stage TNBC..

Keytruda是第一个也是唯一一个基于免疫疗法的方案，作为化疗的新辅助治疗，OS显示出统计学上显着且临床上有意义的改善，然后作为单一药物作为辅助治疗，与安慰剂加化疗相比，随后是高风险早期TNBC患者术后的安慰剂。。

In pre-specified exploratory subgroup analyses of OS, the benefit of the Keytruda regimen was consistent across pre-specified subgroups, including those defined by PD-L1 expression, tumor size and nodal status.

在预先指定的OS探索性亚组分析中，Keytruda方案的益处在预先指定的亚组中是一致的，包括由PD-L1表达，肿瘤大小和淋巴结状态定义的亚组。

“These impactful overall survival results add to the previously reported pathological complete response and event-free survival data from the KEYNOTE-522 trial,” said Dr. Peter Schmid, lead, Centre for Experimental Cancer Medicine, Barts Cancer Institute in London, England. “In this study, pembrolizumab plus chemotherapy as neoadjuvant treatment and continued as a single agent after surgery reduced the risk of death by more than one-third compared to neoadjuvant chemotherapy, reinforcing the important role this regimen plays in the treatment of high-risk early-stage triple-negative breast cancer.”.

英国伦敦巴特斯癌症研究所实验癌症医学中心负责人彼得·施密德博士说：“这些有影响的总体生存结果增加了先前报道的KEYNOTE-522试验的病理完全缓解和无事件生存数据。”。“在这项研究中，pembrolizumab联合化疗作为新辅助治疗，并在手术后继续作为单一药物，与新辅助化疗相比，死亡风险降低了三分之一以上，强化了该方案在治疗高危早期三阴性乳腺癌中的重要作用。”。

“Keytruda is the first and only immunotherapy-based regimen to show a statistically significant and clinically meaningful improvement in overall survival compared to chemotherapy alone in patients with high-risk early-stage triple-negative breast cancer,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories.

默克研究实验室（Merck Research Laboratories）全球临床开发副总裁古塞尔·阿克坦（Gursel Aktan）博士说：“与单独化疗相比，Keytruda是第一个也是唯一一个基于免疫疗法的方案，在高危早期三阴性乳腺癌患者的总生存率方面显示出统计学上显着且具有临床意义的改善。”。

“This is an important milestone and represents the fourth Keytruda study to demonstrate a significant overall survival benefit in an earlier stage of cancer, highlighting our efforts to help extend the lives of patients with certain cancers across different stages of disease.”.

“这是一个重要的里程碑，代表了Keytruda的第四项研究，该研究证明了癌症早期的总体生存获益显着，突出了我们在不同疾病阶段帮助延长某些癌症患者寿命的努力。”。

KEYNOTE-522 is one of four Phase III studies of a Keytruda-based regimen in an earlier stage of cancer to demonstrate an OS benefit, including KEYNOTE-A18 in newly diagnosed, high-risk locally advanced cervical cancer (as treatment with chemoradiotherapy, compared to chemoradiotherapy), KEYNOTE-671 in resectable stage II, IIIA or IIIB non-small cell lung cancer (as treatment with chemotherapy before surgery and then as a single agent after surgery, compared to pre-operative chemotherapy) and KEYNOTE-564 in renal cell carcinoma for patients at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions (compared to placebo)..

KEYNOTE-522是癌症早期基于Keytruda方案的四项III期研究之一，以证明OS的益处，包括KEYNOTE-A18在新诊断的高风险局部晚期宫颈癌中的应用（与放化疗相比，放化疗），KEYNOTE-671在可切除的II期，IIIA期或IIIB期非小细胞肺癌中的应用（与术前化疗相比，术前化疗，术后单药治疗）和KEYNOTE-564在肾癌中的应用，用于肾切除术后或肾切除术后和转移性病变切除术后复发风险较高的患者（与安慰剂相比）。。

As previously announced, the KEYNOTE-522 trial met its dual primary endpoints of pCR and event-free survival (EFS) at earlier interim analyses. Based on these results, KEYTRUDA is approved in the U.S. in combination with chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant treatment after surgery for the treatment of patients with high-risk early-stage TNBC.

如前所述，KEYNOTE-522试验在早期的中期分析中达到了pCR和无事件生存（EFS）的双重主要终点。基于这些结果，KEYTRUDA在美国被批准与化疗联合作为新辅助治疗，然后在手术后继续作为单一药物作为辅助治疗，用于治疗高危早期TNBC患者。

KEYNOTE-522 also supported regulatory approvals for certain patients with TNBC in Europe, Japan and other countries globally..

KEYNOTE-522还支持欧洲，日本和全球其他国家对某些TNBC患者的监管批准。。

As announced , data spanning more than 20 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the ESMO Congress 2024.

正如所宣布的那样，在2024年ESMO大会上，默克公司广泛的肿瘤学投资组合和研究渠道提供了跨越20多种癌症的数据。

Study design and additional data from KEYNOTE-522

来自KEYNOTE-522的研究设计和附加数据

KEYNOTE-522 is a Phase III, randomized, double-blind trial (ClinicalTrials.gov, NCT03036488 ) evaluating Keytruda in combination with chemotherapy as pre-operative (neoadjuvant) treatment and then continuing as a single agent after surgery (adjuvant) compared to placebo plus chemotherapy as neoadjuvant treatment followed by placebo as adjuvant treatment in patients with high-risk early-stage TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC).

KEYNOTE-522是一项III期随机双盲试验（ClinicalTrials.gov，NCT03036488），评估Keytruda联合化疗作为术前（新辅助）治疗，然后在手术后继续作为单一药物（辅助）与安慰剂加化疗作为新辅助治疗相比，随后安慰剂作为高危早期TNBC患者的辅助治疗（每个AJCC的T1c N1-2或T2-4 N0-2期）。

The dual primary endpoints were pCR rate, defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery, and EFS, defined as the time from randomization to the time of first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer or death from any cause.

双重主要终点是pCR率，定义为确定性手术时的病理分期ypT0/Tis ypN0，以及EFS，定义为从随机化到首次发生排除确定性手术的疾病进展的时间，局部/远处复发，第二原发癌或任何原因导致的死亡。

A key secondary endpoint was OS. The study enrolled 1,174 patients who were randomized 2:1 to receive either:  i. The Keytruda regimen: Keytruda  plus chemotherapy (paclitaxel and carboplatin), followed by Keytruda plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as neoadjuvant therapy prior to surgery, followed by Keytruda monotherapy as adjuvant therapy post-surgery (n=784), or; ii.

一个关键的次要终点是操作系统。该研究招募了1174名患者，他们以2:1的比例随机接受：。；二。

The chemotherapy-placebo regimen: Placebo plus chemotherapy (paclitaxel and carboplatin), followed by placebo plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as neoadjuvant therapy prior to surgery, followed by placebo monotherapy as adjuvant therapy post-surgery (n=390)..

化疗安慰剂方案：安慰剂加化疗（紫杉醇和卡铂），然后安慰剂加化疗（环磷酰胺和阿霉素或表柔比星）作为手术前的新辅助治疗，然后安慰剂单药治疗作为手术后的辅助治疗（n=390）。。

After a median follow-up of 75.1 months (range, 65.9-84.0), the Keytruda regimen reduced the risk of EFS events by 35% (HR=0.65 [95% CI, 0.51-0.83]) in patients with high-risk early-stage TNBC compared to the chemotherapy-placebo regimen. The five-year EFS rate was 81.2% (95% CI, 78.3-83.8) for those treated with the Keytruda regimen compared to 72.2% (95% CI, 67.4-76.4) for those treated with the chemotherapy-placebo regimen..

中位随访75.1个月（范围65.9-84.0）后，与化疗安慰剂方案相比，Keytruda方案将高危早期TNBC患者的EFS事件风险降低了35%（HR=0.65[95%CI，0.51-0.83]）。接受Keytruda方案治疗的患者的五年EFS率为81.2%（95%CI，78.3-83.8），而接受化疗安慰剂方案治疗的患者的五年EFS率为72.2%（95%CI，67.4-76.4）。。

At this analysis, treatment-related adverse events (TRAEs) were examined in the neoadjuvant phase, the adjuvant phase and the combined phases. TRAEs in the neoadjuvant phase have been previously reported. At the time of this data cutoff, no patients were still receiving protocol treatment. For the combined neoadjuvant and adjuvant phases, TRAEs occurred in 98.9% of patients receiving the Keytruda regimen (n=783) and 99.7% of patients receiving the chemotherapy-placebo regimen (n=389); Grade 3-5 TRAEs occurred in 82.4% versus 78.7%, respectively.

在此分析中，在新辅助阶段，辅助阶段和联合阶段检查了治疗相关不良事件（TRAE）。先前已经报道了新辅助阶段的TRAE。在数据截止时，没有患者仍在接受方案治疗。对于联合新辅助和辅助阶段，接受Keytruda方案（n=783）的患者中有98.9%发生TRAE，接受化疗安慰剂方案（n=389）的患者中有99.7%发生TRAE；3-5级TRAE发生率分别为82.4%和78.7%。

TRAEs led to death in 0.5% of patients receiving the Keytruda regimen (n=4) and 0.3% of patients receiving the chemotherapy-placebo regimen (n=1). No new safety concerns were identified..

TRAEs导致0.5%接受Keytruda方案（n=4）的患者死亡，0.3%接受化疗安慰剂方案（n=1）的患者死亡。没有发现新的安全问题。。

Immune-mediated adverse events (AEs) and infusion reactions of any grade in the combined neoadjuvant and adjuvant phases occurred in 44.8% of patients receiving the Keytruda regimen and 22.9% of patients receiving the chemotherapy-placebo regimen. The most common of these events (occurring in greater than10% of patients) were infusion reactions (18.0%) and hypothyroidism (15.1%) in patients receiving the Keytruda regimen and infusion reactions (11.6%) in patients receiving the chemotherapy-placebo regimen.

44.8%接受Keytruda方案的患者和22.9%接受化疗安慰剂方案的患者在新辅助和辅助阶段联合发生免疫介导的不良事件（AE）和任何级别的输注反应。这些事件中最常见的（发生在超过10%的患者中）是接受Keytruda方案的患者的输注反应（18.0%）和甲状腺功能减退（15.1%），以及接受化疗安慰剂方案的患者的输注反应（11.6%）。

Immune-mediated AEs led to death in 0.3% of patients receiving the Keytruda regimen (n=2) and no patients receiving the chemotherapy-placebo regimen..

免疫介导的AE导致0.3%接受Keytruda方案（n=2）的患者死亡，而没有接受化疗安慰剂方案的患者死亡。。

Citation: 'Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.' Authors: Peter Schmid, M.D., Javier Cortes, M.D., Rebecca Dent, M.D., Heather McArthur, M.D., Lajos Pusztai, M.D., Sherko Kümmel, M.D., Carsten Denkert, M.D., +16, for the KEYNOTE-522 Investigators*.. NEJM.

作者：医学博士彼得·施密德（PeterSchmid），医学博士哈维尔·科尔特斯（JavierCortes），医学博士丽贝卡·登特（RebeccaDent），医学博士希瑟·麦克阿瑟（HeatherMcArthur），医学博士拉霍斯·普斯泰（LajosPusztai），医学博士谢尔科·库梅尔（SherkoKümmel），医学博士卡斯滕·登科特（CarstenDenkert），医学博士，+16，作为KEYNOTE-522调查员*。。内杰姆。

Published September 15, 2024.

2024年9月15日出版。

Condition: Breast Cancer Triple Neg

条件：乳腺癌三阴性

Type: drug

类型：药物