Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (2): 254-260. doi: 10.19723/j.issn.1671-167X.2020.02.010

Previous Articles     Next Articles

Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice

Guo-hong SONG1,Hui-ping LI1,(),Li-jun DI1,Ying YAN1,Han-fang JIANG1,Ling XU2,Dong-gui WAN3,Ying LI4,Mo-pei WANG5,Yu XIAO5,Ru-yan ZHANG1,Ran RAN1,Huan WANG1   

  1. 1. Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education; Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
    2. Breast Disease Center, Peking University First Hospital, Beijing 100034, China
    3. Department of TCM Oncology, China-Japan Friendship Hospital, Beijing 100029, China
    4. Department of Oncology, General Hospital of PLA, Beijing 100853, China
    5. Department of Tumor Chemotherapy and Radiation Sickness, Peking University Third Hospital, Beijing 100191, China
  • Received:2019-12-26 Online:2020-04-18 Published:2020-04-18
  • Contact: Hui-ping LI E-mail:huipingli2012@hotmail.com

RICH HTML

  

Abstract:

Objective: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase Ⅱ and phase Ⅲ randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world.Methods: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated.Results: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (±trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. Objectiveresponse and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3.Conclusion:Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

Key words: Pyrotinib, Receptor, epidermal growth factor, Breast neoplasms, Trastuzumab, Lapatinib

CLC Number: 

  • R737.9

Table 1

Baseline demographic and disease characteristics of 72 patients"

Items Data
Age
Median/years 55
Range/years 32-79
<65 years, n (%) 64 (88.9)
≥65 years, n (%) 8 (11.1)
Histologic type, n (%)
Invasive ductal 70 (97.2)
Others 2 (2.8)
Hormone receptor status, n (%)
Negative ER and PR 39 (54.2)
Positive ER and/or positive PR 33 (45.8)
Stage at first diagnosis of breast cancer, n (%)
Ⅰ-Ⅲ 59 (81.9)
13 (18.1)
Sites of metastases, n (%)
Visceral 58 (80.6)
Liver 31 (43.1)
Lung 30 (41.7)
Brain 15 (20.8)
Nonvisceral 14 (19.4)
Previous anti-HER2 treatment, n (%)
Yes 69 (95.8)
(Neo) adjuvant setting* 31 (43.1)
Metastatic setting 61 (84.7)
No 3 (4.2)
Prior anti-HER2 therapy for metastases disease, n (%)
Trastuzumab 56 (77.8)
Lapatinib 36 (50.0)
T-DM1 4 (5.6)
No 11 (15.3)
Primary resistant to trastuzumab therapy, n (%)
Yes 26 (36.1)
No 46 (63.9)
Previous lines of chemotherapy in metastatic setting
Median, n 2
0, n (%) 7 (9.7)
1, n (%) 19 (26.4)
2, n (%) 11 (15.3)
≥3, n (%) 35 (48.6)

Table 2

Subgroup analysis of short term response"

Agents Total, n (%) Response, n (%) ORR, n (%) DCR, n (%)
CR PR SD PD
Total 72 (100.0) 1 (1.4) 18 (25.0) 41 (56.9) 12 (16.7) 19 (26.4) 60 (83.3)
Pyrotinib+chemotherapy (±trastuzumab)
Pyrotinib+capecitabine 40 (55.6) 1 (2.5) 13 (32.5) 20 (50.0) 6 (15.0) 14 (35.0) 34 (85.0)
Pyrotinib+vinorelbine (oral) 12 (16.7) 0 (0) 0 (0) 9 (75.0) 3 (25.0) 0 (0) 9 (75.0)
Pyrotinib+etoposide (oral) 4 (5.6) 0 (0) 1 (25.0) 2 (50.0) 1 (25.0) 1 (25.0) 3 (75.0)
Pyrotinib+gemcitabine 2 (2.8) 0 (0) 0 (0) 2 (100.0) 0 (0) 0 (0) 2 (100.0)
Pyrotinib+paclitaxel 1 (1.4) 0 (0) 0 (0) 1 (100.0) 0 (0) 0 (0) 1 (100.0)
Pyrotinib+albumin-bound paclitaxel 1 (1.4) 0 (0) 0 (0) 1 (100.0) 0 (0) 0 (0) 1 (100.0)
Pyrotinib+trastuzumab+gemcitabine 1 (1.4) 0 (0) 1 (100.0) 0 (0) 0 (0) 1 (100.0) 1 (100.0)
Pyrotinib+trastuzumab+albumin-bound paclitaxel 1 (1.4) 0 (0) 0 (0) 0 (0) 1 (100.0) 0 (0) 0 (0)
Pyrotinib+endocrine therapy (±trastuzumab)
Pyrotinib+endocrine therapy 3 (4.2) 0 (0) 1 (33.3) 2 (66.7) 0 (0) 1 (33.3) 3 (100.0)
Pyrotinib+trastuzumab+endocrine therapy 3 (4.2) 0 (0) 2 (66.7) 1 (33.3) 0 (0) 2 (66.7) 3 (100.0)
Pyrotinib (±trastuzumab)
Pyrotinib alone 3 (4.2) 0 (0) 0 (0) 2 (66.7) 1 (33.3) 0 (0) 2 (66.7)
Pyrotinib+trastuzumab 1 (1.4) 0 (0) 0 (0) 1 (100.0) 0 (0) 0 (0) 1 (100.0)

Figure 1

Progression free survival (PFS) of 72 patients"

Figure 2

Progression free survival (PFS) of 36 patients with prior lapatinib therapy"

Figure 3

Progression free survival (PFS) of 15 patients with brain metastasis"

Table 3

Treatment related toxicities of 72 patients"

Toxicity All grades, n (%) Grade, n (%)
1 2 3 4
Diarrhea 57 (79.2) 26 (36.1) 22 (30.6) 9 (12.5) 0 (0)
Neutropenia 16 (22.2) 11 (15.3) 4 (5.6) 1 (1.4) 0 (0)
Anemia 9 (12.5) 4 (5.6) 5 (6.9) 0 (0) 0 (0)
Thrombocytopenia 2 (2.8) 0 (0) 2 (2.8) 0 (0) 0 (0)
Hand-foot syndrome 5 (6.9) 2 (2.8) 0 (0) 3 (4.2) 0 (0)
Rash 2 (2.8) 0 (0) 2 (2.8) 0 (0) 0 (0)
Fatigue 2 (2.8) 1 (1.4) 1 (1.4) 0 (0) 0 (0)
Increased ALT/AST 6 (8.3) 5 (6.9) 1 (1.4) 0 (0) 0 (0)
Increased TBIL 7 (9.7) 7 (9.7) 0 (0) 0 (0) 0 (0)

Table 4

Dose adjustments of pyrotinib in 72 patients"

Starting dose Total, n (%) Dose adjustments
400 mg 65 (90.3) Reduction to 320 mg (n=11)
Reduction to 240 mg (n=2)
Reduction to 160 mg (n=1)
320 mg 7 (9.7) Increase to 400 mg (n=1)
Reduction to 160 mg (n=1)
[1] Slamon DJ, Clark GM, Wong SG , et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene[J]. Science, 1987,235(4785):177-182.
[2] Xu B, Hu X, Zheng H , et al. Outcomes of re-treatment with first-line trastuzumab plus a taxane in HER2 positive metastatic breast cancer patients after (neo) adjuvant trastuzumab: A prospective multicenter study[J]. Oncotarget, 2016,7(31):50643-50655.
[3] Cobleigh M, Yardley D, Brufsky AM , et al. Baseline characteristics, treatment patterns, and outcomes in patients with HER2-positive metastatic breast cancer by hormone receptor status from SystHERs[J]. Clin Cancer Res, 2020,26(5):1105-1113.
[4] Ma F, Li Q, Chen S , et al. Phase I study and biomarker analysis of pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer[J]. J Clin Oncol, 2017,35(27):3105-3112.
[5] Li Q, Guan X, Chen S , et al. Safety, efficacy, and biomarker analysis of pyrotinib in combination with capecitabine in HER2-positive metastatic breast cancer patients: a phase Ⅰ clinical trial[J]. Clin Cancer Res, 2019,25(17):5212-5220.
[6] Ma F, Ouyang Q, Li W , et al. Pyrotinib or lapatinib combined with capecitabine in HER2-positive metastatic breast cancer with prior taxanes, anthracyclines, and/or trastuzumab: a randomized, phase Ⅱ study[J]. J Clin Oncol, 2019,37(29):2610-2619.
[7] Jiang ZF, Yan M, Hu XC , et al. Pyrotinib combined with capecitabine in women with HER2+ metastatic breast cancer previously treated with trastuzumab and taxanes: A randomized phase Ⅲ study[J]. J Clin Oncol, 2019,37(15 suppl):1001.
[8] Wong H, Leung R, Kwong A , et al. Integrating molecular mechanisms and clinical evidence in the management of trastuzumab resistant or refractory HER-2 + metastatic breast cancer [J]. Oncologist, 2011,16(11):1535-1546.
[9] Dawood S, Broglio K, Buzdar AU , et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review[J]. J Clin Oncol, 2010,28(1):92-98.
[10] Slamon DJ, Leyland-Jones B, Shak S , et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2[J]. N Engl J Med, 2001,344(11):783-792.
[11] Burstein HJ, Keshaviah A, Baron AD , et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study[J]. Cancer, 2007,110(5):965-972.
[12] Robert N, Leyland-Jones B, Asmar L , et al. Randomized phase Ⅲ study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpres-sing metastatic breast cancer[J]. J Clin Oncol, 2006,24(18):2786-2792.
[13] Geyer CE, Forster J, Lindquist D , et al. Lapatinib plus capeci-tabine for HER2-positive advanced breast cancer[J]. N Engl J Med, 2006,355(26):2733-2743.
[14] Cameron D, Casey M, Oliva C , et al. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase Ⅲ randomized trial[J]. Oncologist, 2010,15(9):924-934.
[15] Xu BH, Jiang ZF, Chua D , et al. Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients[J]. Chin J Cancer, 2011,30(5):327-335.
[16] Baselga J, Cortés J, Kim SB , Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer[J]. N Engl J Med, 2012,366(2):109-119.
[17] Verma S, Miles D, Gianni L , et al. Trastuzumab emtansine for HER2-positive advanced breast cancer[J]. N Engl J Med, 2012,367(19):1783-1791.
[18] Leyland-Jones B . Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases[J]. J Clin Oncol, 2009,27(31):5278-5286.
[19] Ramakrishna N, Temin S, Chandarlapaty S , et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline[J]. J Clin Oncol, 2014,32(19):2100-2108.
[20] Ramakrishna N, Temin S, Chandarlapaty S , et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: ASCO clinical practice guideline update[J]. J Clin Oncol, 2018,36(27):2804-2807.
[21] Bachelot T, Romieu G, Campone M , et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study[J]. Lancet Oncol, 2013,14(1):64-71.
[22] Montemurro F, Ellis P, Delaloge S, et al. Safety and efficacy of trastuzumab emtansine(>T-DM1) in 399 patients with central nervous system metastases: Exploratory subgroup analysis from the KAMILLA study[J].Cancer Res, 2017, 77(4 Suppl):P1-12-10.
[1] Ying TANG, Yongbo ZHANG, Danhong WU, Yanhong LIN, Fenghua LAN. Detection of pathogenic gene mutations in thirteen cases of congenital bilateral absence of vas deferens infertility patients [J]. Journal of Peking University (Health Sciences), 2024, 56(5): 763-774.
[2] Jian-xun MA,You-chen XIA,Bi LI,Hong-mei ZHAO,Yu-tao LEI,Xi BU. Choice of immediate breast reconstructive methods after modified radical mastectomy [J]. Journal of Peking University (Health Sciences), 2023, 55(4): 612-618.
[3] Yun-jing ZHANG,Li-ying QIAO,Meng QI,Ying YAN,Wei-wei KANG,Guo-zhen LIU,Ming-yuan WANG,Yun-feng XI,Sheng-feng WANG. Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia [J]. Journal of Peking University (Health Sciences), 2023, 55(3): 471-479.
[4] Xiao-juan ZHU,Hong ZHANG,Shuang ZHANG,Dong LI,Xin LI,Ling XU,Ting LI. Clinicopathological features and prognosis of breast cancer with human epidermal growth factor receptor 2 low expression [J]. Journal of Peking University (Health Sciences), 2023, 55(2): 243-253.
[5] Fang CHENG,Shao-ying YANG,Xing-xing FANG,Xuan WANG,Fu-tao ZHAO. Role of the CCL28-CCR10 pathway in monocyte migration in rheumatoid arthritis [J]. Journal of Peking University (Health Sciences), 2022, 54(6): 1074-1078.
[6] Yue WANG,Shuang ZHANG,Hong ZHANG,Li LIANG,Ling XU,Yuan-jia CHENG,Xue-ning DUAN,Yin-hua LIU,Ting LI. Clinicopathological features and prognosis of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer [J]. Journal of Peking University (Health Sciences), 2022, 54(5): 853-862.
[7] Xiao-jing CHENG,Dong JIANG,Lian-hai ZHANG,Jiang-hua WANG,Ya-zhen LI,Jia-hui ZHAI,Bao-qi YAN,Lu-lu ZHANG,Xing-wang XIE,Zi-yu LI,Jia-fu JI. Preclinical study of T cell receptor specifically reactive with KRAS G12V mutation in the treatment of malignant tumors [J]. Journal of Peking University (Health Sciences), 2022, 54(5): 884-895.
[8] Zhi-qing LI,Bing YU,Ze-yu CAI,Ying-bao WANG,Xu ZHANG,Biao ZHOU,Xiao-hong FANG,Fang YU,Yi FU,Jin-peng SUN,Wei LI,Wei KONG. Naringenin inhibits thoracic aortic aneurysm formation in mice with Marfan syndrome [J]. Journal of Peking University (Health Sciences), 2022, 54(5): 896-906.
[9] Tian-yu CAI,Zhen-peng ZHU,Chun-ru XU,Xing JI,Tong-de LV,Zhen-ke GUO,Jian LIN. Expression and significance of fibroblast growth factor receptor 2 in clear cell renal cell carcinoma [J]. Journal of Peking University (Health Sciences), 2022, 54(4): 628-635.
[10] GU Yang-chun,LIU Ying,XIE Chao,CAO Bao-shan. Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases [J]. Journal of Peking University (Health Sciences), 2022, 54(2): 369-375.
[11] TIAN Jia-yi,ZHANG Xia,CHENG Gong,LIU Qing-hong,WANG Shi-yang,HE Jing. Serum interleukin-2 receptor α as a clinical biomarker in patients with systemic lupus erythematosus [J]. Journal of Peking University (Health Sciences), 2021, 53(6): 1083-1087.
[12] LIAO Xu-he,WANG Rong-fu,LIU Meng,CHEN Xue-qi,XIONG Yan,NONG Lin,YIN Lei,ZHANG Bing-ye,DU Yu-jing. Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma [J]. Journal of Peking University (Health Sciences), 2021, 53(2): 246-254.
[13] Xiao-peng ZHANG,Wei-yu ZHANG,Fei HUO,Hao HU,Qi WANG,Ke-xin XU. Outcome of surgical management and pathogenesis of female primary bladder neck obstruction [J]. Journal of Peking University(Health Sciences), 2019, 51(6): 1052-1055.
[14] Xue-jun LIANG,Li-ying GONG,Fei ZHOU,De-min ZHOU,Jing-jing ZHU. Pharmacological effects of site specific conjugated anti-human epidermal growth factor receptor 2-antibody drug conjugate using unnatural amino acid technology [J]. Journal of Peking University(Health Sciences), 2019, 51(5): 797-804.
[15] Xin-yun YAO,Xiao-min GAO,Xiao-ying ZOU,Lin YUE. Role of endocytosis in cell surface CXC chemokine receptor 4 expression of stem cells from apical papilla [J]. Journal of Peking University(Health Sciences), 2019, 51(5): 893-899.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!