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2017年，美国麻省医学会《新英格兰医学杂志》发表的APHINITY研究中位随访45个月结果表明，帕妥珠单抗＋曲妥珠单抗＋化疗，与曲妥珠单抗＋化疗相比，可显著改善HER2阳性早期乳腺癌患者的无浸润病变生存，浸润病变或死亡风险减少19%（风险比：0.81，95%置信区间：0.66～1.00，P=0.045），尤其对于淋巴结阳性或激素受体阴性乳腺癌。从而，APHINITY与NEOSPHERE和CLEOPATRA研究一起实现了帕妥珠单抗用于早期乳腺癌术后、术前和晚期乳腺癌的大满贯。 相关链接 2021年2月4日，美国临床肿瘤学会旗下《临床肿瘤学杂志》在线发表比利时布鲁塞尔自由大学、国际乳腺协作组、列日大学、英国罗氏制药、苏格兰前沿科学基因会、美国德克萨斯大学MD安德森癌症中心、杜克大学、哈佛大学、达纳法伯癌症研究所、波士顿前沿科学基金会、瑞士罗氏总部、澳大利亚乳腺癌研究协作组、加文医学研究所、悉尼大学、法国波尔多大学、中国台湾卫生研究院、台北荣民总医院、波兰医学研究生教育中心、日本京都大学、丹麦哥本哈根大学王国医院、韩国成均馆大学三星首尔医院、德国汉诺威妇科肿瘤医院、哈雷维滕贝格马丁路德大学、意大利米兰大学欧洲肿瘤研究所、巴西国家癌症研究所的APHINITY研究6年随访结果，对HER2阳性早期乳腺癌术后帕妥珠单抗＋曲妥珠单抗＋化疗的总生存和无浸润病变生存进行了第二次中期分析。 APHINITY (NCT01358877): A Randomized Multicenter, Double-Blind, Placebo-Controlled Comparison of Chemotherapy Plus Trastuzumab Plus Placebo Versus Chemotherapy Plus Trastuzumab Plus Pertuzumab as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer (BIG 4-11) 该国际多中心双盲安慰剂随机对照三期临床研究于2011年11月～2013年8月从全球42个国家或地区545家医院入组淋巴结阳性或高风险淋巴结阴性集中确认HER2阳性乳腺癌术后患者4804例，按1∶1的比例随机分为两组，分别给予标准术后化疗＋曲妥珠单抗＋帕妥珠单抗或安慰剂。 结果，中位随访74.1个月，帕妥珠单抗（2400例）与安慰剂（2404例）相比：
对于淋巴结阳性患者，帕妥珠单抗（1503例）与安慰剂（1502例）相比：
对于淋巴结阴性患者，帕妥珠单抗（897例）与安慰剂（902例）相比：
对于激素受体阳性患者，帕妥珠单抗（1536例）与安慰剂（1546例）相比：
对于激素受体阴性患者，帕妥珠单抗（864例）与安慰剂（858例）相比：
两个治疗组的原发心脏事件发生率仍然<1%，未见新的安全问题。 因此，该研究第二次中期分析结果表明，对于HER2阳性早期乳腺癌，尤其淋巴结阳性患者，帕妥珠单抗可显著提高术后标准辅助治疗的无浸润病变生存获益，仍然需要更长的随访时间对总生存获益完成评定，预计将于2022年或发生至少640例死亡事件后进行最终分析。 J Clin Oncol. 2021 Feb 4. Online ahead of print. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Institut Jules Bordet and L'Université Libre de Bruxelles (ULB), Brussels, Belgium; Breast International Group (BIG), Brussels, Belgium; CHU Liege and Liege University, Liege, Belgium; Frontier Science Scotland Ltd, Kincraig, Kingussie, United Kingdom; Roche Products Limited, Welwyn Garden City, United Kingdom; University of Texas, MD Anderson Cancer Center, Huston, TX; Duke Cancer Institute, Duke University, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Harvard TH Chan School of Public Health, Frontier Science Foundation, Boston, MA; Hoffmann-La Roche Ltd, Basel, Switzerland; Breast Cancer Trials Group, Newcastle, Australia; Garvan Institute of Research, Sydney, Australia; Westmead Hospital, Sydney; University of Sydney, Sydney, Australia; Institute Bergonié, UNICANCER, University of Bordeaux, Bordeaux, France; National Health Research Institutes, Taipei, Taiwan; Taipei-Veterans General Hospital, Taipei, Taiwan; Postgraduate Medical Education Center, Warsaw, Poland; Kyoto University Hospital, Kyoto, Japan; Rigshospitalet, University Hospital, Copenhagen, Denmark; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Gynakologisch-Onkologische Praxis Hannover, Hannover, Germany; Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany; University of Milan, European Institute of Oncology, Milan, Italy; Instituto Nacional de Cancer, Rio de Janeiro, Brazil. PURPOSE: APHINITY, at 45 months median follow-up, showed that pertuzumab added to adjuvant trastuzumab and chemotherapy significantly improved invasive disease-free survival (IDFS) (hazard ratio 0.81 [95% CI, 0.66 to 1.00], P = .045) for patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), specifically those with node-positive or hormone receptor (HR)-negative disease. We now report the preplanned second interim overall survival (OS) and descriptive updated IDFS analysis with 74 months median follow-up. METHODS: After surgery and central HER2-positive confirmation, 4,805 patients with node-positive or high-risk node-negative BC were randomly assigned (1:1) to either 1-year pertuzumab or placebo added to standard adjuvant chemotherapy and 1-year trastuzumab. RESULTS: This interim OS analysis comparing pertuzumab versus placebo did not reach the P = .0012 level required for statistical significance (P = .17, hazard ratio 0.85). Six-year OS were 95% versus 94% with 125 deaths (5.2%) versus 147 (6.1%), respectively. IDFS analysis based on 508 events (intent-to-treat population) showed a hazard ratio of 0.76 (95% CI, 0.64 to 0.91) and 6-year IDFS of 91% and 88% for pertuzumab and placebo groups, respectively. The node-positive cohort continues to derive clear IDFS benefit from pertuzumab (hazard ratio 0.72 [95% CI, 0.59 to 0.87]), 6-year IDFS being 88% and 83%, respectively. Benefit was not seen in the node-negative cohort. In a subset analysis, IDFS benefit from pertuzumab showed a hazard ratio of 0.73 (95% CI, 0.59 to 0.92) for HR-positive disease and a hazard ratio of 0.83 (95% CI, 0.63 to 1.10) for HR-negative disease. Primary cardiac events remain < 1% in both the treatment groups. No new safety signals were seen. CONCLUSION: This analysis confirms the IDFS benefit from adding pertuzumab to standard adjuvant therapy for patients with node-positive HER2-positive early BC. Longer follow-up is needed to fully assess OS benefit. PMID: 33539215 DOI: 10.1200/JCO.20.01204
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