Zhimin Shao1, Da Pang2, Hongjian Yang3, Wei Li4, Shusen Wang5, Shude Cui6, Ning Liao7, Yongsheng Wang8, Chuan Wang9, Yuan-Ching Chang10, Hweichung Wang11, Seok Yun Kang12, Jae Hong Seo13, Kunwei Shen14, Suphawat Laohawiriyakamol15, Zefei Jiang16, Junjie Li1, Julian Zhou17, Betsy Althaus18, Yixiang Mao19,20, Jennifer Eng-Wong18. 1. Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 2. Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China. 3. Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, China. 4. Medicine-Oncology, The First Hospital of Jilin University, Changchun, China. 5. Medicine-Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. 6. Department of Breast Disease, Henan Cancer Hospital, Zhengzhou, China. 7. Department of Breast Disease, Guangdong General Hospital, Guangzhou, China. 8. Breast Disease Center, Shandong Cancer Hospital, Jinan, China. 9. Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, China. 10. Department of General Surgery, Mackay Memorial Hospital, Taipei City, Taiwan. 11. Department of Surgery, China Medical University Hospital, Taichung City, Taiwan. 12. Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Republic of Korea. 13. Division of Oncology/Hematology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. 14. Breast Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 15. Department of Surgery, Songklanagarind Hospital, Songkhla, Thailand. 16. Medicine-Oncology, The Affiliated Hospital of Military Medical Sciences (The 307th Hospital of Chinese People's Liberation Army), Beijing, China. 17. Biometrics, Roche Product Development, Shanghai, China. 18. Product Development Oncology, Genentech, Inc, South San Francisco, California. 19. Roche Product Development, Shanghai, China. 20. now at Oncology Clinical Research, Merck Sharp & Dohme China, Shanghai, China.
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. Trial Registration: ClinicalTrials.gov identifier: NCT02586025.
RCT Entities:
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. Trial Registration: ClinicalTrials.gov identifier: NCT02586025.
Authors: Benjamin James Hall; Ajay Ashok Bhojwani; Helen Wong; Andrea Law; Helen Flint; Eliyaz Ahmed; Helen Innes; Joanne Cliff; Zaf Malik; Julie Elizabeth O'Hagan; Allison Hall; Rajaram Sripadam; Shaun Tolan; Zulfiqar Ali; Clare Hart; Douglas Errington; Farida Alam; Rosa Giuliani; Shaveta Mehta; Sheena Khanduri; Nicky Thorp; Richard Jackson; Silvia Cicconi; Carlo Palmieri Journal: Breast J Date: 2022-06-30 Impact factor: 2.269