Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study
Abstract The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive br...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02138-6 |
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| author | Fei Wang Yongjiu Wang Bin Xiong Zhenlin Yang Jingfen Wang Yumin Yao Lixiang Yu Qinye Fu Liang Li Qiang Zhang Chao Zheng Shuya Huang Liyuan Liu Chun Liu Huaibo Sun Beibei Mao Dong-Xu Liu Zhigang Yu |
| author_facet | Fei Wang Yongjiu Wang Bin Xiong Zhenlin Yang Jingfen Wang Yumin Yao Lixiang Yu Qinye Fu Liang Li Qiang Zhang Chao Zheng Shuya Huang Liyuan Liu Chun Liu Huaibo Sun Beibei Mao Dong-Xu Liu Zhigang Yu |
| author_sort | Fei Wang |
| collection | DOAJ |
| description | Abstract The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab (TCbH). Early response was assessed using magnetic resonance imaging (MRI) after two cycles of treatment. Patients showing poor response, as defined by RECIST 1.1, could opt to receive additional pyrotinib or continue standard therapy. The primary endpoint was the total pathological complete response (tpCR; ypT0/isN0) rate. Of the 129 patients enroled, 62 (48.1%) were identified as MRI-responders (cohort A), 26 non-responders continued with four more cycles of TCbH (cohort B), and 41 non-responders received additional pyrotinib (cohort C). The tpCR rate was 30.6% (95% CI: 20.6–43.0%) in cohort A, 15.4% (95% CI: 6.2–33.5%) in cohort B, and 29.3% (95% CI: 17.6–44.5%) in cohort C. Multivariable logistic regression analyses demonstrated comparable odds of achieving tpCR between cohorts A and C (odds ratio = 1.04, 95% CI: 0.40–2.70). No new adverse events were observed with the addition of pyrotinib. Patients with co-mutations of TP53 and PIK3CA exhibited lower rates of early partial response compared to those without or with a single gene mutation (36.0% vs. 60.0%, P = 0.08). These findings suggest that adding pyrotinib may benefit patients who do not respond to neoadjuvant trastuzumab plus chemotherapy. Further investigation is warranted to identify biomarkers predicting patients’ benefit from the addition of pyrotinib. |
| format | Article |
| id | doaj-art-80be45bb02f0473cafc2abf34f81f895 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-80be45bb02f0473cafc2abf34f81f8952025-02-02T12:44:33ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-01-011011910.1038/s41392-025-02138-6Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted studyFei Wang0Yongjiu Wang1Bin Xiong2Zhenlin Yang3Jingfen Wang4Yumin Yao5Lixiang Yu6Qinye Fu7Liang Li8Qiang Zhang9Chao Zheng10Shuya Huang11Liyuan Liu12Chun Liu13Huaibo Sun14Beibei Mao15Dong-Xu Liu16Zhigang Yu17Breast Center, The Second Hospital of Shandong UniversityBreast Center, The Second Hospital of Shandong UniversityDepartment of Breast Surgery, Affiliated Hospital of Jining Medical UniversityDepartment of Breast Surgery, Binzhou Medical University HospitalDepartment of Breast Surgery, Linyi Cancer HospitalDepartment of Breast Surgery, Liaocheng People’s HospitalBreast Center, The Second Hospital of Shandong UniversityBreast Center, The Second Hospital of Shandong UniversityBreast Center, The Second Hospital of Shandong UniversityBreast Center, The Second Hospital of Shandong UniversityBreast Center, The Second Hospital of Shandong UniversityBreast Center, The Second Hospital of Shandong UniversityBreast Center, The Second Hospital of Shandong UniversityGenecast Biotechnology Co.Ltd.Genecast Biotechnology Co.Ltd.Genecast Biotechnology Co.Ltd.Breast Center, The Second Hospital of Shandong UniversityBreast Center, The Second Hospital of Shandong UniversityAbstract The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab (TCbH). Early response was assessed using magnetic resonance imaging (MRI) after two cycles of treatment. Patients showing poor response, as defined by RECIST 1.1, could opt to receive additional pyrotinib or continue standard therapy. The primary endpoint was the total pathological complete response (tpCR; ypT0/isN0) rate. Of the 129 patients enroled, 62 (48.1%) were identified as MRI-responders (cohort A), 26 non-responders continued with four more cycles of TCbH (cohort B), and 41 non-responders received additional pyrotinib (cohort C). The tpCR rate was 30.6% (95% CI: 20.6–43.0%) in cohort A, 15.4% (95% CI: 6.2–33.5%) in cohort B, and 29.3% (95% CI: 17.6–44.5%) in cohort C. Multivariable logistic regression analyses demonstrated comparable odds of achieving tpCR between cohorts A and C (odds ratio = 1.04, 95% CI: 0.40–2.70). No new adverse events were observed with the addition of pyrotinib. Patients with co-mutations of TP53 and PIK3CA exhibited lower rates of early partial response compared to those without or with a single gene mutation (36.0% vs. 60.0%, P = 0.08). These findings suggest that adding pyrotinib may benefit patients who do not respond to neoadjuvant trastuzumab plus chemotherapy. Further investigation is warranted to identify biomarkers predicting patients’ benefit from the addition of pyrotinib.https://doi.org/10.1038/s41392-025-02138-6 |
| spellingShingle | Fei Wang Yongjiu Wang Bin Xiong Zhenlin Yang Jingfen Wang Yumin Yao Lixiang Yu Qinye Fu Liang Li Qiang Zhang Chao Zheng Shuya Huang Liyuan Liu Chun Liu Huaibo Sun Beibei Mao Dong-Xu Liu Zhigang Yu Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study Signal Transduction and Targeted Therapy |
| title | Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study |
| title_full | Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study |
| title_fullStr | Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study |
| title_full_unstemmed | Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study |
| title_short | Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study |
| title_sort | neoadjuvant pyrotinib and trastuzumab in her2 positive breast cancer with no early response neopather efficacy safety and biomarker analysis of a prospective multicentre response adapted study |
| url | https://doi.org/10.1038/s41392-025-02138-6 |
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