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

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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

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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)
Ⅳ 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)
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