De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trialResearch in context
Summary: Background: Due to the undesirable cumulative toxicity of multiple drugs, de-escalated neoadjuvant chemotherapy strategies are needed for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pyrotinib, a small-molecule irreversible pan-HER receptor tyrosine kinase inhibi...
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Elsevier
2025-08-01
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| author | Hong Pan Yi Ren Mengyao Zha Mingduo Liu Xiaoan Liu Hui Xie Xiaoming Zha Yi Zhao Lin Chen Tiansong Xia Zhao Liu Jing Tao Hua Pan Yue Sun Wei Li Cong Wang Qiang Ding Shui Wang Wenbin Zhou |
| author_facet | Hong Pan Yi Ren Mengyao Zha Mingduo Liu Xiaoan Liu Hui Xie Xiaoming Zha Yi Zhao Lin Chen Tiansong Xia Zhao Liu Jing Tao Hua Pan Yue Sun Wei Li Cong Wang Qiang Ding Shui Wang Wenbin Zhou |
| author_sort | Hong Pan |
| collection | DOAJ |
| description | Summary: Background: Due to the undesirable cumulative toxicity of multiple drugs, de-escalated neoadjuvant chemotherapy strategies are needed for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pyrotinib, a small-molecule irreversible pan-HER receptor tyrosine kinase inhibitor, shows promising efficacy in the neoadjuvant setting. We aimed to determine the efficacy, safety and predictive biomarkers of the de-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer. Methods: In this multicenter phase 2 study (NCT05659056), patients who were histologically diagnosed with HER2-positive breast cancer (clinical stage ⅡA–ⅢC) were deemed suitable to participate in this study. Participants received pyrotinib (400 mg once), trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg maintenance dose), and nab-paclitaxel (260 mg/m2) on day 1 of each 3-week cycle for six cycles. The primary endpoint was the rate of total pathological complete response (tpCR) among BluePrint HER2-enriched breast cancers, which was defined as complete disappearance of invasive tumor in breast specimen and all sampled axillary lymph nodes (ypT0/is, ypN0). This study has been completed. Findings: Between 3 December 2022 and 6 June 2024, 74 participants were finally enrolled in the study. Of all enrolled participants, 66 had baseline BluePrint and MammaPrint results. Among the 43 participants with BluePrint HER2-enriched breast cancer, 23 achieved tpCR (53%, 95% CI 38%–69%), and 28 achieved breast pathological complete response (bpCR) (65%, 95% CI 49%–79%). Among the 23 participants with non-HER2-enriched subtypes, 7 achieved tpCR (30%, 95% CI 13%–53%), while 10 achieved bpCR (43%, 95% CI 23%–66%). Of 66 participants with MammaPrint risk score index, the tpCR rate in MammaPrint ultra-high group (24/39) was significantly higher than that in high group (6/27, P = 0.0024). With the median follow-up of 19.9 months (IQR, 15.5–25.4), no cases of recurrence, metastasis, or mortality events were observed. Grade 3–4 treatment-related adverse events occurred in 17 (23%) participants. The most common grade 3–4 adverse event was diarrhea (10/74). No treatment-related deaths occurred. Of all enrolled participants, no treatment discontinuations occurred due to disease progression during the neoadjuvant therapy period. Interpretation: De-escalated neoadjuvant cytotoxic chemotherapy regimen is promising for BluePrint HER2-enriched breast cancer. Our results provide critical references for the efficacy and biomarkers of de-escalated neoadjuvant therapy in HER2-positive breast cancer. Funding: National Natural Science Foundation of China and Natural Science Foundation of Jiangsu Province. |
| format | Article |
| id | doaj-art-d4998e2650d942c484488d3f87fe1621 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-08-01 |
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| series | EClinicalMedicine |
| spelling | doaj-art-d4998e2650d942c484488d3f87fe16212025-08-20T03:28:17ZengElsevierEClinicalMedicine2589-53702025-08-018610337610.1016/j.eclinm.2025.103376De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trialResearch in contextHong Pan0Yi Ren1Mengyao Zha2Mingduo Liu3Xiaoan Liu4Hui Xie5Xiaoming Zha6Yi Zhao7Lin Chen8Tiansong Xia9Zhao Liu10Jing Tao11Hua Pan12Yue Sun13Wei Li14Cong Wang15Qiang Ding16Shui Wang17Wenbin Zhou18Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Breast and Thyroid Surgery, The Affiliated Huai’an First People’s Hospital of Nanjing Medical University, Huai’an, ChinaDepartment of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Thyroid and Breast Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of General Surgery, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, Liyang Branch of Jiangsu Provincial People’s Hospital, Liyang, ChinaDepartment of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, ChinaDepartment of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Corresponding author. Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Corresponding author. Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Corresponding author. Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Corresponding author. Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.Summary: Background: Due to the undesirable cumulative toxicity of multiple drugs, de-escalated neoadjuvant chemotherapy strategies are needed for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pyrotinib, a small-molecule irreversible pan-HER receptor tyrosine kinase inhibitor, shows promising efficacy in the neoadjuvant setting. We aimed to determine the efficacy, safety and predictive biomarkers of the de-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer. Methods: In this multicenter phase 2 study (NCT05659056), patients who were histologically diagnosed with HER2-positive breast cancer (clinical stage ⅡA–ⅢC) were deemed suitable to participate in this study. Participants received pyrotinib (400 mg once), trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg maintenance dose), and nab-paclitaxel (260 mg/m2) on day 1 of each 3-week cycle for six cycles. The primary endpoint was the rate of total pathological complete response (tpCR) among BluePrint HER2-enriched breast cancers, which was defined as complete disappearance of invasive tumor in breast specimen and all sampled axillary lymph nodes (ypT0/is, ypN0). This study has been completed. Findings: Between 3 December 2022 and 6 June 2024, 74 participants were finally enrolled in the study. Of all enrolled participants, 66 had baseline BluePrint and MammaPrint results. Among the 43 participants with BluePrint HER2-enriched breast cancer, 23 achieved tpCR (53%, 95% CI 38%–69%), and 28 achieved breast pathological complete response (bpCR) (65%, 95% CI 49%–79%). Among the 23 participants with non-HER2-enriched subtypes, 7 achieved tpCR (30%, 95% CI 13%–53%), while 10 achieved bpCR (43%, 95% CI 23%–66%). Of 66 participants with MammaPrint risk score index, the tpCR rate in MammaPrint ultra-high group (24/39) was significantly higher than that in high group (6/27, P = 0.0024). With the median follow-up of 19.9 months (IQR, 15.5–25.4), no cases of recurrence, metastasis, or mortality events were observed. Grade 3–4 treatment-related adverse events occurred in 17 (23%) participants. The most common grade 3–4 adverse event was diarrhea (10/74). No treatment-related deaths occurred. Of all enrolled participants, no treatment discontinuations occurred due to disease progression during the neoadjuvant therapy period. Interpretation: De-escalated neoadjuvant cytotoxic chemotherapy regimen is promising for BluePrint HER2-enriched breast cancer. Our results provide critical references for the efficacy and biomarkers of de-escalated neoadjuvant therapy in HER2-positive breast cancer. Funding: National Natural Science Foundation of China and Natural Science Foundation of Jiangsu Province.http://www.sciencedirect.com/science/article/pii/S2589537025003086Breast cancerHER2PyrotinibNeoadjuvant therapy |
| spellingShingle | Hong Pan Yi Ren Mengyao Zha Mingduo Liu Xiaoan Liu Hui Xie Xiaoming Zha Yi Zhao Lin Chen Tiansong Xia Zhao Liu Jing Tao Hua Pan Yue Sun Wei Li Cong Wang Qiang Ding Shui Wang Wenbin Zhou De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trialResearch in context EClinicalMedicine Breast cancer HER2 Pyrotinib Neoadjuvant therapy |
| title | De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trialResearch in context |
| title_full | De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trialResearch in context |
| title_fullStr | De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trialResearch in context |
| title_full_unstemmed | De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trialResearch in context |
| title_short | De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trialResearch in context |
| title_sort | de escalated neoadjuvant nab paclitaxel combined with pyrotinib and trastuzumab in intrinsic her2 enriched breast cancer njmu bc01 a multicenter single arm phase 2 trialresearch in context |
| topic | Breast cancer HER2 Pyrotinib Neoadjuvant therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2589537025003086 |
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