Pivotal results from the Phase 3 BREAKWATER trial showed 51% risk reduction in death compared to standard-of-care treatment

关键的3期BREAKWATER试验结果表明，与标准治疗相比，死亡风险降低了51%。

BRAFTOVI combination regimen also demonstrated 47% risk reduction in disease progression or death compared to standard-of-care treatment, meeting the trial’s dual primary endpoint of progression-free survival

BRAFTOVI联合治疗方案与标准治疗相比，还显示了疾病进展或死亡风险降低了47%，达到了试验的无进展生存期的双重主要终点。

First and only combination regimen with targeted therapy to improve survival outcomes for treatment-naïve patients with BRAF V600E-mutant metastatic colorectal cancer

首个也是唯一一个联合靶向疗法的治疗方案，可改善BRAF V600E突变的转移性结直肠癌初治患者的生存结果。

NEW YORK--(BUSINESS WIRE)--

纽约--（商业资讯）--

Pfizer Inc. (NYSE: PFE) today announced statistically significant and clinically meaningful survival results from the Phase 3 BREAKWATER trial evaluating BRAFTOVI

辉瑞公司（纽约证券交易所代码：PFE）今天宣布了三期 BREAKWATER 试验的统计学显著且具有临床意义的生存结果，该试验评估了 BRAFTOVI。

(encorafenib) in combination with cetuximab (marketed as ERBITUX

(encorafenib) 联合西妥昔单抗（商品名：ERBITUX）

) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) with a

) 和 mFOLFOX6（氟尿嘧啶、亚叶酸钙和奥沙利铂）用于治疗转移性结直肠癌 (mCRC) 患者，具有

BRAF V600E

BRAF V600E

mutation. These data will be presented today in an oral presentation (Abstract LBA3500) at the 2025 American Society of Clinical Oncology (ASCO

这些数据将在2025年美国临床肿瘤学会（ASCO）的今天的一个口头报告（摘要号LBA3500）中展示。

) Annual Meeting and have been simultaneously published in the

）年度会议，并同时发布在

New England Journal of Medicine

新英格兰医学杂志

In a second interim analysis of overall survival (OS), a key secondary endpoint, the BRAFTOVI combination regimen reduced the risk of death by 51% compared to standard-of-care chemotherapy with or without bevacizumab (Hazard Ratio [HR] 0.49; 95% Confidence Interval [CI], 0.38, 0.63, p<0.0001). Median OS was 30.3 months (95% CI, 21.7, Not Estimated) with BRAFTOVI.

在对总生存期（OS）这一关键次要终点的第二次中期分析中，与含或不含贝伐单抗的标准护理化疗相比，BRAFTOVI联合治疗方案将死亡风险降低了51%（风险比[HR] 0.49；95%置信区间[CI]，0.38, 0.63，p<0.0001）。使用BRAFTOVI的中位总生存期为30.3个月（95% CI，21.7，未估计）。

in combination with cetuximab and mFOLFOX6 compared to 15.1 months with chemotherapy with or without bevacizumab (95% CI, 13.7, 17.7). In the primary analysis of progression-free survival (PFS), the BRAFTOVI combination regimen reduced the risk of disease progression or death by 47% compared to standard-of-care chemotherapy with or without bevacizumab (HR 0.53; 95% CI, 0.41, 0.68, p<0.0001) as assessed by blinded independent central review (BICR).

与西妥昔单抗和mFOLFOX6联合使用相比，化疗加或不加贝伐珠单抗的中位无进展生存期为15.1个月（95% CI，13.7, 17.7）。在无进展生存期（PFS）的主要分析中，根据盲法独立中心审查（BICR）评估，BRAFTOVI联合方案相较于加或不加贝伐珠单抗的标准治疗化疗，将疾病进展或死亡的风险降低了47%（HR 0.53；95% CI，0.41, 0.68，p<0.0001）。

Median PFS was 12.8 months (95% CI, 11.2, 15.9) with the BRAFTOVI combination regimen compared to 7.1 months (95% CI, 6.8, 8.5)..

BRAFTOVI联合治疗方案的中位PFS为12.8个月（95% CI，11.2，15.9），相比之下为7.1个月（95% CI，6.8，8.5）。

“Patients with metastatic colorectal cancer whose tumors harbor a

“肿瘤中存在转移性结直肠癌患者的”

BRAF V600E

BRAF V600E突变

mutation generally face a daunting prognosis, as this aggressive tumor often does not respond well to standard-of-care chemotherapy,” said Elena Élez, M.D., Ph.D., senior investigator at Vall d’Hebron Institute of Oncology in Barcelona, Spain, and co-principal investigator of the BREAKWATER trial. “The BREAKWATER results are the first promising survival outcomes ever reported for .

突变通常面临严峻的预后，因为这种侵袭性肿瘤通常对标准治疗化疗反应不佳，”西班牙巴塞罗那瓦尔德希伯伦肿瘤研究所高级研究员、BREAKWATER试验的联合首席研究员埃琳娜·埃莱兹医学博士说道。“BREAKWATER的结果是迄今为止报道的首个有希望的生存结果。

BRAF

BRAF

-mutant metastatic colorectal cancer in the first-line setting, representing a practice-changing breakthrough for patients.”

-突变型转移性结直肠癌的一线治疗，为患者带来了改变实践的突破。”

CRC is the third most common type of cancer in the world

结直肠癌是世界第三大常见癌症类型。

mutations are estimated to occur in 8-12% of people with mCRC and represent a poor prognosis.

估计有8-12%的mCRC患者会发生突变，代表预后较差。

BRAF V600E

BRAF V600E

mutation is the most common

变异是最常见的

BRAF

BRAF

mutation and the risk of mortality in patients with CRC harboring this mutation is more than double that of patients with no known

突变以及携带该突变的结直肠癌患者的死亡风险是无已知突变患者的两倍多

BRAF

BRAF

mutation present.

存在突变。

2-4

2-4

“The BRAFTOVI combination helped significantly reduce the risk of disease progression or death, potentially altering the course of disease for people with metastatic colorectal cancer with a

“BRAFTOVI组合显著降低了疾病进展或死亡的风险，可能改变携带特定基因变异的转移性结直肠癌患者的病程。”

BRAF V600E

BRAF V600E

The updated objective response rate (ORR) by BICR confirmed the improvement previously observed with the BRAFTOVI combination regimen compared to patients receiving chemotherapy with or without bevacizumab (65.7%; 95% CI, 59.4, 71.4 and 37.4%; 95% CI, 31.6, 43.7, respectively). The estimated median duration of response and median time to response were also maintained from the prior primary analysis.

根据BICR确认的更新客观缓解率（ORR）显示，与接受化疗联合或不联合贝伐珠单抗的患者相比，BRAFTOVI联合方案之前观察到的改善得到了进一步验证（分别为65.7%；95% CI，59.4, 71.4 和 37.4%；95% CI，31.6, 43.7）。预估的中位缓解持续时间和中位缓解时间也与之前的初步分析结果保持一致。

Results from the primary analysis of ORR were presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCO GI) and were simultaneously published in .

ORR主要分析结果在2025年美国临床肿瘤学会胃肠道癌症研讨会（ASCO GI）上公布，并同时发表于。

Nature Medicine

自然医学

in January 2025. Additional data from a separate arm of the BREAKWATER study evaluating BRAFTOVI in combination with cetuximab will also be presented at ASCO.

2025年1月。BREAKWATER研究另一部分评估BRAFTOVI与西妥昔单抗联合使用的更多数据也将在ASCO会议上展示。

“The risk of death for patients with

“对于患者来说，死亡的风险

BRAF V600E

BRAF V600E

-mutant metastatic colorectal cancer is more than double compared to those with no known mutation,” said Michael Sapienza, Chief Executive Officer, Colorectal Cancer Alliance. “These survival outcomes from the BREAKWATER study bring renewed hope to patients and their loved ones, providing the possibility of more time together.

“与没有已知突变的患者相比，突变型转移性结直肠癌的生存率高出两倍以上，”结直肠癌联盟首席执行官迈克尔·萨皮恩扎表示。“BREAKWATER研究的这些生存结果为患者及其亲人带来了新的希望，提供了更多共处的时间可能。”

We are thrilled to see important cancer research propel us closer to our goal of ending this disease.”.

我们很高兴看到重要的癌症研究推动我们更接近终结这种疾病的目标。”

At the time of this analysis, the safety profile of BRAFTOVI in combination with cetuximab and mFOLFOX6 continued to be consistent with the known safety profile of each respective agent. No new safety signals were identified. The most common side effects (≥30%) were nausea, anemia, diarrhea, decreased appetite, vomiting, neutrophil count decrease, arthralgia, and rash.

在本次分析时，BRAFTOVI联合西妥昔单抗和mFOLFOX6的安全性特征仍然与每种药物已知的安全性特征一致。未发现新的安全性信号。最常见的副作用（≥30%）为恶心、贫血、腹泻、食欲减退、呕吐、中性粒细胞计数减少、关节痛和皮疹。

Among patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6, 13.8% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI..

在联合使用BRAFTOVI、西妥昔单抗和mFOLFOX6的患者中，有13.8%的患者发生了导致永久停用BRAFTOVI的不良反应。

The BRAFTOVI combination regimen received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2024 for patients with

BRAFTOVI联合治疗方案于2024年12月获得美国食品药品监督管理局（FDA）的加速批准，用于治疗

BRAF V600E

BRAF V600E

-mutant mCRC based on a clinically meaningful and statistically significant improvement in confirmed ORR in treatment-naïve patients, the study’s other dual primary endpoint.

-mutant mCRC 基于初治患者中确认的 ORR 获得临床意义和统计学显著性改善，这是该研究的另一个双重主要终点。

Continued approval for this indication is contingent upon verification of clinical benefit. The approval was among the first in the industry to be conducted under the FDA’s Project FrontRunner, which seeks to support the development and approval of new cancer drugs for advanced or metastatic disease.

对该适应症的持续批准取决于临床益处的验证。此次批准是行业内首批在FDA的“前沿计划”下进行的，该计划旨在支持针对晚期或转移性疾病的新型癌症药物的研发和批准。

The BREAKWATER survival data are being discussed with the U.S. FDA to support potential conversion to full approval in 2025..

BREAKWATER的生存数据正在与美国FDA讨论，以支持在2025年可能转为完全批准。

Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented, which are written in non-technical language. Those interested in learning more can visit

辉瑞公司将继续致力于帮助非科学家理解最新的研究成果，正在开发公司赞助研究的摘要通俗语言总结 (APLS)，这些总结使用非技术性语言撰写。有兴趣了解更多的人可以访问