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Mini Oral session: Breast cancer, metastatic

LBA19 - Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer (PHILA): A randomized phase III trial


10 Sep 2022


Mini Oral session: Breast cancer, metastatic



Tumour Site

Breast Cancer


Binghe Xu


Annals of Oncology (2022) 33 (suppl_7): S808-S869. 10.1016/annonc/annonc1089


B. Xu1, M. Yan2, F. Ma1, W. Li3, Q. Ouyang4, Z. Tong5, Y. Teng6, S. Wang7, Y. Wang8, C. Geng9, T. Luo10, J. Zhong11, Q. Zhang12, Q. Liu13, X. Zeng14, T. Sun15, Q. Mo16, F. Dong17, S. Wu17, X. Zhu17

Author affiliations

  • 1 Department Of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 - Beijing/CN
  • 2 Department Of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, 450008 - Zhengzhou/CN
  • 3 Department Of Oncology, The First Hospital of Jilin University, 130021 - Changchun/CN
  • 4 Breast Internal Medicine Department, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013 - Changsha/CN
  • 5 Department Of Breast Oncology, Tianjin Medical University Cancer Institute & Hospital, 300060 - Tianjin/CN
  • 6 Department Of Breast Internal Medicine, The First Hospital of China Medical University, 110001 - Shenyang/CN
  • 7 Department Of Internal Medicine, Sun Yat-sen University Cancer Center, 510060 - Guangzhou/CN
  • 8 Breast Surgery, Shandong Cancer Hospital & Institute, 250117 - Jinan/CN
  • 9 Breast Center, The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital, 50011 - Shijiazhuang/CN
  • 10 Department Of Medical Oncology Of Cancer Center, West China Hospital, Sichuan University, 610041 - Chengdu/CN
  • 11 Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, 530021 - Nanning/CN
  • 12 Medical Oncology Department, Cancer Hospital Harbin Medical University, 150040 - Harbin/CN
  • 13 Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 - Guangzhou/CN
  • 14 Breast Cancer Center, Affiliated Cancer Hospital of Chongqing University, 400000 - Chongqing/CN
  • 15 Breast Internal Medicine Department, Liaoning Cancer Hospital & Institute, 110042 - Shenyang/CN
  • 16 Breast Surgery, Guangxi Medical University Affiliated Tumor Hospital, Nanning/CN
  • 17 Department Of Clinical Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., 200120 - Shanghai/CN


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Abstract LBA19


Pyrotinib (pyro, an irreversible pan-HER inhibitor) plus capecitabine has demonstrated antitumor activity as 2L treatment in HER2-positive metastatic breast cancer (mBC) (Lancet Oncol 2021). Pertuzumab combined with trastuzumab (H) and docetaxel (T) is the standard 1L dual anti-HER2 therapy for HER2-positive mBC. Here, we report the efficacy and safety of dual anti-HER2 regimen of Pyro+H+T (PyroHT) compared with placebo+H+T (HT) in untreated HER2-positive mBC.


Eligible pts were randomized (1:1) to receive oral Pyro (400 mg QD) or placebo, both combined with intravenous H (8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles) and T (75 mg/m2) on day 1 of each 21-day cycle. The primary endpoint was PFS per investigator (INV). Data cutoff for this prespecified interim analysis was May 25, 2022.


Between May 2019 and Jan 2022, 590 eligible pts from 40 centers were randomized and treated (297 with PyroHT and 293 with HT). Median follow-up was 15.8 mo and 14.9 mo, respectively. PFS per INV of PyroHT was significantly longer than HT (median, 24.3 mo [95% CI 19.1-33.0] vs 10.4 mo [95% CI 9.3-12.3]; HR, 0.41 [95% CI 0.32-0.53]; P < 0.0001; subgroup results are in Table 1), which was consistent with PFS per IRC (median, 33.0 vs 10.4 mo; HR, 0.35 [95% CI 0.27-0.46]). The most common grade ≥3 TRAEs were decreased neutrophil count (62.6% vs 65.2%), decreased WBC count (53.2% vs 50.9%), and diarrhea (46.5% vs 3.1%). Grade 3 diarrhea occurred mainly during cycle 1 and substantially decreased in cycle 2 and thereafter. No grade 4 or 5 diarrheas occurred. Serious TRAEs occurred in 24.9% vs 6.1% of pts and treatment-related deaths occurred in 0 vs 0.3% of pts, respectively. Table: LBA19

Subgroup analyses of PFS per INV

PyroHT HT HR (95% CI)
n/N PFS (median, mo) n/N PFS (median, mo)
ECOG performance status
0 55/164 27.5 96/155 10.4 0.42 (0.30-0.59)
1 44/133 22.2 82/138 10.3 0.39 (0.27-0.57)
Prior neoadjuvant or adjuvant therapy
Yes 49/148 27.8 91/153 10.6 0.43 (0.30-0.62)
No 50/149 19.5 87/140 10.3 0.38 (0.26-0.54)
Prior neoadjuvant or adjuvant trastuzumab
Yes 11/46 NA 32/42 9.3 0.23 (0.12-0.46)
No 88/251 21.9 146/251 10.4 0.45 (0.34-0.59)
Treatment-free interval with prior adjuvant therapy
≥12 - <24 mo 8/30 NA 25/38 8.3 0.22 (0.10-0.50)
≥24 mo 34/99 22.2 58/100 13.0 0.57 (0.37-0.87)

n/N=events/patients. HRs are from unstratified analyses.


PyroHT significantly prolonged PFS over HT in pts with HER2-positive mBC. The safety is manageable. To our knowledge, this is the second phase 3 trial to demonstrate PFS benefit from dual HER2 inhibition in 1L treatment of HER2-positive mBC.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.


Jiangsu Hengrui Pharmaceuticals Co., Ltd.


B. Xu: Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Roche, Eisai; Financial Interests, Personal, Advisory Role: Roche.. F. Dong: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd. S. Wu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Zhu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd. All other authors have declared no conflicts of interest.

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