Trastuzumab

IGCC 2025微专辑扫描二维码可查看更多内容编者按目前晚期胃癌的化疗方案选择众多，如何为患者优选最佳治疗方案尚未达成共识。在第16届国际胃癌大会（IGCC）上，布雷西亚大学的Silvia Ministrini教授介绍了聚焦Ⅳ期胃癌新型化疗方案的MetaGastro研究主要结果，会后，肿瘤瞭望消化时讯邀请Ministrini教授进行深入解析。肿瘤瞭望消化时讯：MetaGastro研究聚焦于Ⅳ期胃癌的新型化疗方案，能否详细阐述该方案的核心创新点？Ministrini教授：我们尝试在该注册研究中比较不同化疗方案的疗效差异，但遗憾的是目前尚未发现它们之间存在显著的统计学差异，这主要源于当前入组患者的数量不足，不过我们可以观察到单药治疗或HER2靶向治疗等新方案在生存获益方面呈现更优的趋势。我们的注册研究仍在持续入组患者，因此有望在不久的将来重复此项分析并获得显著性结论。同样地，针对化疗耐药性问题，现有数据尚不足以支持深入探讨。Dr Ministrini: We tried to compare the results of different chemotherapy regimens in our registry, but unfortunately, we could not find any statistically significant differences amongst the regimens, mainly because we don’t have enough patients at the moment, but we can see new regimens such as monotherapy or HER2-targeted therapies seem to have better results in terms of survival, although we could not find statistical significance in those differences. Our registry is still recruiting patients, so, we can repeat this analysis in the near future and hope that we can find significant results. The same applies to chemoresistance. With our data, we were not able to elaborate more on this question.肿瘤瞭望消化时讯：您的研究数据显示新方案改善了患者预后。在亚组分析中，是否存在特定分子特征或临床特征显著影响疗效？Ministrini教授：关于转移灶肿瘤负荷的影响，我们观察到不同转移部位患者的生存期无显著差异。此外，多发转移灶患者与单发转移患者的生存期也相似。由此可见，在该研究人群中，转移灶的肿瘤负荷并非影响生存的主要因素。另一方面，HER2表达状态、微卫星稳定性及PD-L1表达水平等分子特征可能影响生存结局，因为这些标志物能为患者提供靶向治疗机会。既往文献证实具有特定分子表达特征的患者可通过靶向治疗获得生存益处，我们的数据也印证了这一趋势，但仍需扩大样本量以增强结论的可信度。Dr Ministrini: Regarding the metastatic burden, we observed that the survival of patients does not differ according to metastasis location. Also, patients with more than one metastatic site have similar survival when compared to single metastatic sites. So, we can say in this population, metastatic burden is not one of the principal factors that influence survival. On the other hand, the presence of HER2 status expression or microsatellite stability or PD-L1 expression are factors that can influence survival, because we can use targeted therapy in these patients. We know from the literature that targeted therapy in patients with a specific molecular expression or status can benefit from targeted therapy and can improve survival. Our data appears to confirm these results, but we need more patients to give stronger confirmation.研究介绍01.1.12-Ⅳ期胃癌的新化疗方案——来自MetaGastro的数据背景:研究分析了意大利Ⅳ期胃癌的注册数据MetaGastro，以评估采用的不同化疗方案。方法：进行描述性统计以评估不同的治疗方案，同时通过Kaplan Meyer曲线评估对生存的影响。结果：2024年6月，数据库共筛选出538例转移性胃癌患者，其中57例接受最佳支持治疗；27例因症状接受了前期手术；454例被安排进行全身治疗：409例接受了化疗，40例接受了化学免疫治疗，5例由于病情迅速恶化而无法开始治疗。最常见的化疗方案包括：Folfox(44.7%)、Flot(20.9%)、化疗+曲妥珠单抗(10.6%)、铂类和卡培他滨(8.9%)、氟尿嘧啶(3.8%)和其他(2.2%)。8.9%的患者使用了化学免疫疗法。对生存有影响的方案包括铂+卡培他滨和氟尿嘧啶单药治疗。生存分析显示化疗、化学免疫疗法和化疗+曲妥珠单抗组之间没有显著差异(P=0.17)。3组的主要并发症率相似：化疗9.8%，化学免疫疗法20%，化疗+曲妥珠单抗26.1%(P=006)。在341例被认为初诊无法手术的患者中有280例接受了化疗，31例接受化学免疫疗法，30例接受化疗+曲妥珠单抗；这3组的转化率分别为18.1%、12.9%和20.0%(P=0.727)。结论：在转移性胃癌患者的人群中，我们发现化疗方案的使用存在很大差异。化学免疫疗法在生存方面没有显示出显著获益，但这些结果可能是由于该治疗亚组的患者数量相对较少。（来源：肿瘤瞭望消化时讯）声 明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

BARCELONA, Spain--(BUSINESS WIRE)--REVEAL GENOMICS, S.L., a biotechnology company advancing precision oncology through biomarker innovation, today announced the presentation of four independent studies at the 2025 ASCO Annual Meeting. The studies, involving more than 800 patients, evaluated the clinical utility of its flagship test, HER2DX, in early-stage HER2-positive (HER2+) breast cancer. The studies presented at the 2025 ASCO Annual Meeting, involving more than 800 patients, evaluated the clinical utility of HER2DX, in early-stage HER2-positive (HER2+) breast cancer. The four studies, CompassHER2 pCR, BionHER, RESPECT and DFCI, validate HER2DX as a powerful genomic tool for predicting response to therapy and long-term prognosis, addressing critical questions. The findings, which provide valuable insights for optimizing treatment strategies in early-stage HER2+ breast cancer and metastatic breast cancer, will be shared in oral and poster sessions led by academic investigators from the U.S., Europe, and Japan. CompassHER2 pCR or EA1181 (U.S.): HER2DX determining response to THP-based de-escalated therapy This study is led by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), a scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer, comprising nearly 1,400 member institutions in the U.S. and around the world. HER2DX was evaluated as a secondary aim as part of a pre-specified, prospectively planned analysis embedded in the CompassHER2 pCR trial, also known as EA1181 (NCT04266249). This large, prospective multicenter phase II trial is assessing neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in more than 2,000 patients with stage II–III HER2+ breast cancer, without the use of anthracyclines, cyclophosphamide, and carboplatin. The HER2DX assay was defined as a key secondary endpoint, with profiling of all available baseline samples planned. Among 569 patients assessed to date for the HER2DX pathologic complete response (pCR) score, those with higher scores achieved significantly greater pCR rates, independent of estrogen receptor (ER) status. These findings confirm the ability of HER2DX to identify tumors more likely to respond to THP. Importantly, additional results are expected from this trial, as patients continue to be followed for the primary endpoints of 3-year survival outcomes, and the study team plans to profile many more baseline samples. “The ability to predict response to THP is extremely valuable,” said Dr. Nadine Tung, Director of Breast Medical Oncology at Beth Israel Deaconess Medical Center, Professor of Medicine at Harvard Medical School, and Principal Investigator of the CompassHER2 pCR (EA1181) trial. “HER2DX provides a biology-driven tool that contributes to the selection of patients who can safely reduce chemotherapy, something we’ve long needed in HER2-positive early breast cancer.” “It is encouraging to see the assay’s performance in both ER-positive and ER-negative subgroups,” added Dr. Tung. “The plan is to profile all available samples from the trial, and these early data already provide valuable insights for guiding treatment selection.” BionHER trial (Spain): Validation of HER2DX-guided de-escalation strategy The BionHER phase II trial (NCT05912062) evaluated HER2DX in 83 patients with stage I–III HER2+ breast cancer treated with neoadjuvant THP for up to 15 weeks at the Catalan Institute of Oncology (ICO L’Hospitalet, Barcelona, Spain). HER2DX was successfully performed in all baseline FFPE tumor samples. The HER2DX pCR score was significantly associated with pCR with a performance AUC of 0.835. Patients classified by HER2DX pCR score into low, medium, and high groups had increasing pCR rates of 13.3%, 51.6%, and 81.8%, respectively. HER2DX outperformed traditional biomarkers, such as ER, Ki-67, and tumor-infiltrating lymphocytes, in predicting pCR. “HER2DX is transforming the way we approach treatment selection in HER2-positive disease,” said Dr. Sònia Pernas, head of the breast cancer unit at ICO L’Hospitalet, and Principal Investigator of the BionHER study. “By identifying tumors more likely to respond to dual HER2 blockade with a single taxane, we are increasingly able to personalize treatment intensity without compromising efficacy.” RESPECT trial (Japan): a response for an unrepresented population Trans-RESPECT is a prespecified translational analysis within the Japanese RESPECT non-inferiority trial (NCT01104935), in which 266 patients aged 70–80 years with stage I-III HER2+ breast cancer were randomized to receive adjuvant trastuzumab with or without chemotherapy (Sawaki et al. J Clin Oncol 2020). HER2DX was assessed in 154 of these patients, with a median follow-up of 9.1 years. The HER2DX risk score effectively stratified patients by 10-year relapse-free survival (86.6% in the low-risk group vs. 68.4% in the high-risk group) and overall survival (94.5% vs.72.5%). Notably, chemotherapy conferred an overall survival benefit only in tumors classified as pCR-high by HER2DX, with a significant interaction p-value of 0.045. “HER2DX provided clear long-term prognostic information in this elderly population,” said Dr. Kazuki Nozawa, Lead Investigator of Trans-RESPECT, from the Department of Advanced Clinical Research and Development and the Department of Breast Surgery at Nagoya City University Graduate School of Medical Sciences. “Importantly, its ability to help identify which patients may benefit from adjuvant chemotherapy is highly relevant to clinical decision-making. Older patients with HER2DX low-risk scores, particularly those classified as pCR-low or -medium, appear to be ideal candidates for trastuzumab alone, without chemotherapy.” DFCI T-DXd study (U.S.): predicting survival outcome to T-DXd Dana-Farber Cancer Institute (DFCI) conducted a retrospective analysis of 41 patients with metastatic breast cancer (25 HER2-positive, 16 HER2-negative) treated with trastuzumab deruxtecan (T-DXd) monotherapy between 2017 and 2023. The HER2DX HER2 signature score was significantly associated with time to next treatment (p=0.001). When stratified into tertiles, patients in the highest tertile had a median time to next treatment of 12.03 months compared to 4.7 months in the lowest tertile (p=0.02). “Quantitative measurement of HER2 amplicon expression by HER2DX is a key determinant of T-DXd activity in metastatic breast cancer,” said Dr. Sara M. Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute. She added, “Further evaluation of this genomic test in ongoing T-DXd trials is warranted.” HER2DX makes a significant impact at ASCO 2025 “ASCO 2025 marks a pivotal milestone for HER2DX,” said Dr. Aleix Prat, Chief Scientific Officer and co-founder of REVEAL GENOMICS. “This test is demonstrating clinical value in real-world practice across continents and care settings, assisting in the tailoring of chemotherapy intensity in the neoadjuvant setting and supporting chemotherapy-free decisions in the adjuvant setting.” Patricia Villagrasa, CEO and co-founder, added, “HER2DX was developed with HER2+ disease at its core, and these four high-quality, independent studies reinforce its clinical value. As we continue to grow globally, this is a clear example of how REVEAL GENOMICS is turning cutting-edge science into meaningful solutions that advance personalized cancer care worldwide.” About HER2DX HER2DX is the world’s first diagnostic test formulated specifically for HER2+ breast cancer. Marketed by REVEAL GENOMICS since January 2022, the HER2DX is a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer. HER2DX is a prognostic and predictive assay based on clinical and genomic data. The test integrates clinical information (i.e., tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene. HER2DX®️predicts: Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer. pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery. ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low and HER2+ breast cancer. About REVEAL GENOMICS REVEAL GENOMICS, S.L., together with its U.S. subsidiary REVEAL GENOMICS, Inc., is a biotechnology company dedicated to redefining the role of biomarkers in oncology. The company focuses on developing innovative diagnostic tools that optimize therapeutic decision-making for individuals with cancer. By leveraging advanced genomic technologies, sophisticated computational algorithms, and machine learning, REVEAL GENOMICS generates novel insights into cancer biology and treatment response. academic and clinical institutions to advance precision oncology. REVEAL GENOMICS, S.L. is a spin-off company of Hospital Clínic of Barcelona, IDIBAPS, the University of Barcelona (U.B.), and the Vall d’Hebron Institute of Oncology (VHIO). REVEAL GENOMICS® and HER2DX® are registered trademarks of REVEAL GENOMICS, S.L. For further information visit: http://www.reveal-genomics.com