Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients with Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial

Zhimin Shao, Da Pang, Hongjian Yang, Wei Li, Shusen Wang, Shude Cui, Ning Liao, Yongsheng Wang, Chuan Wang, Yuan Ching Chang, Hweichung Wang, Seok Yun Kang, Jae Hong Seo, Kunwei Shen, Suphawat Laohawiriyakamol, Zefei Jiang, Junjie Li, Julian Zhou, Betsy Althaus, Yixiang MaoJennifer Eng-Wong

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106 Citations (Scopus)

Abstract

Importance: Prospective assessment of treatments known to benefit patients in global clinical trials in specific racial groups is essential. Objective: To compare the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled phase 3 trial enrolled 329 women with ERBB2-positive early (T2-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) and primary tumor larger than 2 cm from March 14, 2016, to March 13, 2017. Analysis of the primary end point was performed on an intention-to-treat basis. Interventions: Before surgery, patients received 4 cycles of intravenous pertuzumab (840-mg loading dose and 420-mg maintenance doses), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), and docetaxel (75 mg/m2) or intravenous placebo, trastuzumab, and docetaxel every 3 weeks. After surgery, patients received 3 cycles of intravenous fluorouracil, epirubicin, and cyclophosphamide followed by 13 cycles of the same intravenous anti-ERBB2 therapy (pertuzumab and trastuzumab or placebo and trastuzumab) for up to 1 year. Main Outcomes and Measures: The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by disease category and hormone receptor status, was used to compare rates between treatment groups. Results: In total, 329 female patients were randomized (pertuzumab, 219; and placebo, 110; mean [SD] age, 48.8 [9.5] years). In the intention-to-treat population, total pathologic complete response rates were 39.3% (86 of 219) in the pertuzumab group and 21.8% (24 of 110) in the placebo group (difference, 17.5% [95% CI, 6.9%-28.0%]; P =.001). Of the most common grade 3 or higher adverse events, there was a higher incidence of neutropenia in the pertuzumab group (83 of 218 [38.1%] vs 36 of 110 [32.7%]). Serious adverse events were reported in 10.1% of patients (22 of 218) in the pertuzumab group and 8.2% of patients (9 of 110) in the placebo group. Conclusions and Relevance: Treatment with pertuzumab, trastuzumab, and docetaxel resulted in a statistically significant improvement in the total pathologic complete response rate vs placebo, trastuzumab, and docetaxel for the neoadjuvant treatment of ERBB2-positive early or locally advanced breast cancer in Asian patients. Safety data were in line with the known pertuzumab safety profile and generally comparable between treatment groups. The PEONY trial adds to the totality of data showing the benefit of the pertuzumab regimen.

Original languageEnglish
JournalJAMA Oncology
Volume6
Issue number3
DOIs
Publication statusPublished - 2020 Mar
Externally publishedYes

Bibliographical note

Funding Information:
receiving support for third-party writing assistance for this manuscript, provided by F. Hoffmann-La Roche Ltd. Dr Shao reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Pang reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Yang reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr W. Li reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr S. Wang reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution) and honoraria (personal). Dr Cui reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Liao reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Y. Wang reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr C. Wang reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Chang reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr H. Wang reported receiving research funding (paid to institution) and lecture fees (personal) from F. Hoffmann-La Roche Ltd. Dr Kang reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Seo reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Shen reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Laohawiriyakamol reported receiving research funding from F. Hoffmann-La Roche Ltd/Genentech, Inc via Roche Thailand Ltd (paid to institution). Dr Jiang reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr J. Li reported receiving research funding from F. Hoffmann-La Roche Ltd (paid to institution). Dr Zhou is an employee of Roche Product Development. Dr Althaus is an employee of Genentech, Inc and owns shares in F. Hoffmann-La Roche Ltd. Dr Mao was an employee of Roche Product Development at the time of the study and owns shares in F. Hoffmann-La Roche Ltd. Dr Eng-Wong is an employee of Genentech, Inc and owns shares in F. Hoffmann-La Roche Ltd. No other disclosures were reported.

Publisher Copyright:
© 2019 American Medical Association. All rights reserved.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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