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对于HER2阳性早期或局部晚期乳腺癌，国际多中心非盲随机对照二期临床研究NEOSPHERE证实术前新辅助治疗加用帕妥珠单抗可显著提高病理完全缓解率，国际多中心安慰剂双盲随机对照三期临床研究APHINITY证实术后辅助治疗加用帕妥珠单抗可显著提高无浸润癌生存率。不过，这些研究都以欧美患者为主。 2024年3月9日，英国《自然》旗下《自然通讯》发表复旦大学附属肿瘤医院黄亮和邵志敏✉️、哈尔滨医科大学附属肿瘤医院庞达、浙江省肿瘤医院杨红健、吉林大学第一医院李薇、中山大学肿瘤防治中心王树森、河南省肿瘤医院崔树德、广东省人民医院廖宁、山东省肿瘤医院王永胜、福建医科大学附属协和医院王川、台北马偕纪念医院张源清、中国医药大学附设医院王惠畅、上海交通大学医学院附属瑞金医院沈坤炜、解放军总医院第五医学中心江泽飞、韩国亚洲大学医院姜锡允、高丽大学九老医院徐在弘、泰国宋卡王子大学素帕瓦·劳哈维里亚莫尔等学者的牡丹（PEONY）研究最终分析报告，首次对亚洲HER2阳性早期或局部晚期乳腺癌术前术后全程帕妥珠单抗与安慰剂＋曲妥珠单抗＋化疗的有效性和安全性进行比较。 PEONY (NCT02586025): Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer to Evaluate Treatment With Trastuzumab Plus (+) Pertuzumab + Docetaxel Compared With Trastuzumab + Placebo + Docetaxel (A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate Pertuzumab in Combination With Docetaxel and Trastuzumab as Neoadjuvant Therapy, and Pertuzumab in Combination With Trastuzumab as Adjuvant Therapy After Surgery and Chemotherapy in Patients With Early-Stage or Locally Advanced HER2-Positive Breast Cancer) 该国际多中心安慰剂双盲随机对照三期临床研究于2016年3月14日至2017年3月13日从中韩泰三国23个医学中心入组HER2阳性早期或局部晚期乳腺癌女性329例，按2∶1随机分为两组： 该研究主要终点为独立评审委员会评定的总体（乳房＋淋巴结）病理完全缓解率，次要终点包括无事件生存、无病变生存、总生存和安全性。 此前对截至2017年10月23日的短期数据进行主要终点分析，帕妥珠组与安慰剂组相比： 此次对截至2022年3月14日中位随访62.9个月的长期数据进行次要终点分析，帕妥珠组与安慰剂组相比： 5年无事件生存率：84.8%比73.7%（提高11.1%，95%置信区间：1.2～21.0，P=0.027；风险比：0.53，95%置信区间：0.32～0.89） 5年无病变生存率：86.0%比75.0%（提高11.0%，95%置信区间：1.2～20.7，P=0.028；风险比：0.52，95%置信区间：0.30～0.88） 5年总生存率：93.9%比90.0%（提高3.9%，95%置信区间：2.9～10.7，P=0.262；风险比：0.53，95%置信区间：0.23～1.19）
此外，根据亚组分析，即使对于残留浸润病变（未获总体病理完全缓解）患者，帕妥珠组与安慰剂组相比，也可获益： 安全性数据与已知的帕妥珠单抗安全性一致，两组不良事件发生率基本相似，除了腹泻（40.8%比17.3%）。 因此，该研究结果表明，对于亚洲HER2阳性早期或局部晚期乳腺癌患者，术前新辅助治疗和术后辅助治疗加入帕妥珠单抗可以显著提高总体病理完全缓解率、5年无事件生存率和5年无病变生存率，获益显著大于风险。 相关链接 Nat Commun. 2024 Mar 9;15:2153. IF: 16.6Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.Huang L, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang HC, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Wang H, Lamour F, Song G, Curran M, Duan C, Lysbet de Haas S, Restuccia E, Shao Z.Fudan University Shanghai Cancer Center, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; Harbin Medical University Cancer Hospital, Harbin, China; Cancer Hospital of The University of Chinese Academy of Sciences, Hangzhou, China; The First Hospital of Jilin University, Changchun, China; Sun Yat-sen University Cancer Center, Guangzhou, China; Henan Cancer Hospital, Zhengzhou, China; Guangdong General Hospital, Guangzhou, China; Shandong Cancer Hospital, Jinan, China; Fujian Medical University Union Hospital, Fuzhou, China; Mackay Memorial Hospital, Taipei City, Taiwan, China; China Medical University Hospital, Taichung City, Taiwan, China; Ajou University School of Medicine, Suwon, Korea; Korea University Guro Hospital, Seoul, Korea; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Prince of Songkla University, Songkhla, Thailand; The Affiliated Hospital of Military Medical Sciences (The 307th Hospital of Chinese. People's Liberation Army), Beijing, China; Roche Product Development, Shanghai, China; F. Hoffmann-La Roche Ltd, Basel, Switzerland; Alentis Therapeutics AG, Allschwil, Switzerland; Hangzhou Tigermed Consulting Co., Ltd, Shanghai, China; Roche (China) Holding Ltd, Shanghai, China.The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.DOI: 10.1038/s41467-024-45591-7
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