Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits
IntroductionPyrotinib is a novel irreversible pan-HER tyrosine kinase inhibitor (TKI). However, real-world data of pyrotinib-containing therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and developing brain metastases (BMs) are limited, and the genomi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1105474/full |
| _version_ | 1827924220296822784 |
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| author | Hui Wang Hui Wang Qiaoyan Liu Mi Zhang Mi Zhang Juan Zhang Juan Zhang Ran Ran Ran Ran Yingying Ma Yingying Ma Jiao Yang Fan Wang Shujuan He Shujuan He Xiaoai Zhao Le Wang Lingxiao Zhang Danfeng Dong Jin Yang Jin Yang |
| author_facet | Hui Wang Hui Wang Qiaoyan Liu Mi Zhang Mi Zhang Juan Zhang Juan Zhang Ran Ran Ran Ran Yingying Ma Yingying Ma Jiao Yang Fan Wang Shujuan He Shujuan He Xiaoai Zhao Le Wang Lingxiao Zhang Danfeng Dong Jin Yang Jin Yang |
| author_sort | Hui Wang |
| collection | DOAJ |
| description | IntroductionPyrotinib is a novel irreversible pan-HER tyrosine kinase inhibitor (TKI). However, real-world data of pyrotinib-containing therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and developing brain metastases (BMs) are limited, and the genomic profile of this subpopulation is almost undefined.Methods and materialsPatients with BM of HER2-positive MBC (n = 35) treated with pyrotinib-containing therapy were enrolled in this analysis. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) for disease progression were estimated using the Cox proportional hazards models. Targeted next-generation sequencing of 618 cancer-relevant genes was performed on plasma and primary breast tumors from patients with BM and without BM.ResultsThe median PFS time was 8.00 (95% CI, 5.98–10.017) months, and the median OS time was 23 (95% CI, 10.412–35.588) months. The ORR was 45.7%, and the DCR was 74.3%. In the Cox multivariate analysis, prior exposure to brain radiotherapy (HR = 3.268), received pyrotinib as third- or higher-line treatment (HR = 4.949), subtentorial brain metastasis (HR = 6.222), and both supratentorial and subtentorial brain metastases (HR = 5.863) were independently associated with increased risk of progression. The frequent grade 3–4 adverse event was increased direct bilirubin (14.3%), and two patients suffered from grade 3–4 diarrhea. In the exploratory genomic analysis, altered frequencies of FGFR3, CD276, CDC73, and EPHX1 were higher in the BM group. The consistency of mutated profiles of plasma and primary lesion in the BM group was significantly lower (30.4% vs. 65.5%; p = 0.0038).ConclusionsPyrotinib-containing therapy shows favorable effectiveness and tolerable safety in patients with BM of HER2-positive MBC, particularly in a population that is brain radiotherapy-naïve, received pyrotinib as first- or second-line treatment, and developed supratentorial brain metastasis. In the exploratory genomic analysis, patients with BM showed distinct genomic features from patients without BM. |
| first_indexed | 2024-03-13T05:08:41Z |
| format | Article |
| id | doaj.art-32085b257e944317a709ffe0a3c6dfaf |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T05:08:41Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-32085b257e944317a709ffe0a3c6dfaf2023-06-16T06:16:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-06-011310.3389/fonc.2023.11054741105474Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraitsHui Wang0Hui Wang1Qiaoyan Liu2Mi Zhang3Mi Zhang4Juan Zhang5Juan Zhang6Ran Ran7Ran Ran8Yingying Ma9Yingying Ma10Jiao Yang11Fan Wang12Shujuan He13Shujuan He14Xiaoai Zhao15Le Wang16Lingxiao Zhang17Danfeng Dong18Jin Yang19Jin Yang20Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Oncology, Xi’an Ninth Hospital, Xi’an, ChinaCancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaIntroductionPyrotinib is a novel irreversible pan-HER tyrosine kinase inhibitor (TKI). However, real-world data of pyrotinib-containing therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and developing brain metastases (BMs) are limited, and the genomic profile of this subpopulation is almost undefined.Methods and materialsPatients with BM of HER2-positive MBC (n = 35) treated with pyrotinib-containing therapy were enrolled in this analysis. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) for disease progression were estimated using the Cox proportional hazards models. Targeted next-generation sequencing of 618 cancer-relevant genes was performed on plasma and primary breast tumors from patients with BM and without BM.ResultsThe median PFS time was 8.00 (95% CI, 5.98–10.017) months, and the median OS time was 23 (95% CI, 10.412–35.588) months. The ORR was 45.7%, and the DCR was 74.3%. In the Cox multivariate analysis, prior exposure to brain radiotherapy (HR = 3.268), received pyrotinib as third- or higher-line treatment (HR = 4.949), subtentorial brain metastasis (HR = 6.222), and both supratentorial and subtentorial brain metastases (HR = 5.863) were independently associated with increased risk of progression. The frequent grade 3–4 adverse event was increased direct bilirubin (14.3%), and two patients suffered from grade 3–4 diarrhea. In the exploratory genomic analysis, altered frequencies of FGFR3, CD276, CDC73, and EPHX1 were higher in the BM group. The consistency of mutated profiles of plasma and primary lesion in the BM group was significantly lower (30.4% vs. 65.5%; p = 0.0038).ConclusionsPyrotinib-containing therapy shows favorable effectiveness and tolerable safety in patients with BM of HER2-positive MBC, particularly in a population that is brain radiotherapy-naïve, received pyrotinib as first- or second-line treatment, and developed supratentorial brain metastasis. In the exploratory genomic analysis, patients with BM showed distinct genomic features from patients without BM.https://www.frontiersin.org/articles/10.3389/fonc.2023.1105474/fullHER2-positive breast cancerbrain metastasespyrotinibclinical benefitsgenomic profile |
| spellingShingle | Hui Wang Hui Wang Qiaoyan Liu Mi Zhang Mi Zhang Juan Zhang Juan Zhang Ran Ran Ran Ran Yingying Ma Yingying Ma Jiao Yang Fan Wang Shujuan He Shujuan He Xiaoai Zhao Le Wang Lingxiao Zhang Danfeng Dong Jin Yang Jin Yang Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits Frontiers in Oncology HER2-positive breast cancer brain metastases pyrotinib clinical benefits genomic profile |
| title | Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits |
| title_full | Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits |
| title_fullStr | Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits |
| title_full_unstemmed | Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits |
| title_short | Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits |
| title_sort | real world data of pyrotinib based therapy for patients with brain metastases of her2 positive advanced breast cancer a single center retrospective analysis and molecular portraits |
| topic | HER2-positive breast cancer brain metastases pyrotinib clinical benefits genomic profile |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1105474/full |
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