Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial
Abstract We aimed to evaluate the efficacy and safety of adding apatinib, to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer (TNBC). In the phase 2 NeoSAC trial, patients with early TNBC received six cycles of apatinib, sintilimab, nab-paclitaxel, and...
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Nature Publishing Group
2025-02-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02137-7 |
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| author | Guoshuang Shen Zhilin Liu Miaozhou Wang Yi Zhao Xinlan Liu Yujin Hou Wenbiao Ma Jingqi Han Xiaofeng Zhou Dengfeng Ren Fuxing Zhao Zitao Li Shifen Huang Yongzhi Chen Yingjian He Yan Liu Zijun Zhu Yongxin Li Jinming Li Mengting Da Hongnan Mo Feng Du Liang Cui Jing Bai Zhen Liu Fei Ma Jiuda Zhao |
| author_facet | Guoshuang Shen Zhilin Liu Miaozhou Wang Yi Zhao Xinlan Liu Yujin Hou Wenbiao Ma Jingqi Han Xiaofeng Zhou Dengfeng Ren Fuxing Zhao Zitao Li Shifen Huang Yongzhi Chen Yingjian He Yan Liu Zijun Zhu Yongxin Li Jinming Li Mengting Da Hongnan Mo Feng Du Liang Cui Jing Bai Zhen Liu Fei Ma Jiuda Zhao |
| author_sort | Guoshuang Shen |
| collection | DOAJ |
| description | Abstract We aimed to evaluate the efficacy and safety of adding apatinib, to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer (TNBC). In the phase 2 NeoSAC trial, patients with early TNBC received six cycles of apatinib, sintilimab, nab-paclitaxel, and carboplatin followed by surgery. The primary endpoint was pathological complete response (pCR) rate. Specimens collected pre-neoadjuvant therapy and post-surgery were retained for comprehensive analysis of predictive biomarkers and the impact on the tumor microenvironment. Among 34 enrolled patients, 24 achieved pCR (70.6%; 95% confidence interval (CI), 53.0-85.3), and 79.4% (95% CI, 65.1-93.7) had residual cancer burden 0-I. Imaging evaluation showed 21 complete responses (61.8%) and 13 partial responses (38.2%). The most common grade 3-4 adverse events were leukopenia (47%), neutropenia (36%), and thrombocytopenia (24%). The 36-month disease-free survival rate stood at 94.1% with a median follow-up of 39.1 months. Notably, baseline high ImmuneScore, immune cell infiltration, and enrichment of interferon-related pathways correlated with pCR. Comparison of pre-neoadjuvant and post-surgery data revealed that the pCR group treated with this novel regimen exhibited an upregulation of distinct immune cell subsets, thereby activating the tumor microenvironment. Moreover, higher oxeiptosis scores were associated with an increased likelihood of achieving pCR. Following neoadjuvant therapy, the pCR group showed a decrease in oxeiptosis score, whereas the non-pCR group exhibited an increase. Our study suggests that apatinib, sintilimab combined with carboplatin and nab-paclitaxel chemotherapy showed a promising clinical activity and manageable safety profile in early TNBC and merits further study. ClinicalTrials.gov registration: NCT04722718. |
| format | Article |
| id | doaj-art-21d6f6946e0b4add802a7023ee485e04 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
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| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-21d6f6946e0b4add802a7023ee485e042025-02-09T12:56:32ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-02-011011910.1038/s41392-025-02137-7Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trialGuoshuang Shen0Zhilin Liu1Miaozhou Wang2Yi Zhao3Xinlan Liu4Yujin Hou5Wenbiao Ma6Jingqi Han7Xiaofeng Zhou8Dengfeng Ren9Fuxing Zhao10Zitao Li11Shifen Huang12Yongzhi Chen13Yingjian He14Yan Liu15Zijun Zhu16Yongxin Li17Jinming Li18Mengting Da19Hongnan Mo20Feng Du21Liang Cui22Jing Bai23Zhen Liu24Fei Ma25Jiuda Zhao26Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityMedical Oncology Department of General Hospital of Ningxia Medical UniversityMedical Oncology Department of General Hospital of Ningxia Medical UniversityDepartment of Oncology, 2nd Ward, Qinghai Provincial People’s Hospital (Breast and Thyroid Surgery)Department of pathology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityDepartment of pathology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityKey laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & InstituteDepartment of Public Health, Medical College of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityState Key Laboratory of Molecular Oncology, Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing),The VIPII Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian DistrictGeneplus-Beijing InstituteGeneplus-Beijing InstituteBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityState Key Laboratory of Molecular Oncology, Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBreast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai UniversityAbstract We aimed to evaluate the efficacy and safety of adding apatinib, to sintilimab and chemotherapy in the neoadjuvant treatment of early triple-negative breast cancer (TNBC). In the phase 2 NeoSAC trial, patients with early TNBC received six cycles of apatinib, sintilimab, nab-paclitaxel, and carboplatin followed by surgery. The primary endpoint was pathological complete response (pCR) rate. Specimens collected pre-neoadjuvant therapy and post-surgery were retained for comprehensive analysis of predictive biomarkers and the impact on the tumor microenvironment. Among 34 enrolled patients, 24 achieved pCR (70.6%; 95% confidence interval (CI), 53.0-85.3), and 79.4% (95% CI, 65.1-93.7) had residual cancer burden 0-I. Imaging evaluation showed 21 complete responses (61.8%) and 13 partial responses (38.2%). The most common grade 3-4 adverse events were leukopenia (47%), neutropenia (36%), and thrombocytopenia (24%). The 36-month disease-free survival rate stood at 94.1% with a median follow-up of 39.1 months. Notably, baseline high ImmuneScore, immune cell infiltration, and enrichment of interferon-related pathways correlated with pCR. Comparison of pre-neoadjuvant and post-surgery data revealed that the pCR group treated with this novel regimen exhibited an upregulation of distinct immune cell subsets, thereby activating the tumor microenvironment. Moreover, higher oxeiptosis scores were associated with an increased likelihood of achieving pCR. Following neoadjuvant therapy, the pCR group showed a decrease in oxeiptosis score, whereas the non-pCR group exhibited an increase. Our study suggests that apatinib, sintilimab combined with carboplatin and nab-paclitaxel chemotherapy showed a promising clinical activity and manageable safety profile in early TNBC and merits further study. ClinicalTrials.gov registration: NCT04722718.https://doi.org/10.1038/s41392-025-02137-7 |
| spellingShingle | Guoshuang Shen Zhilin Liu Miaozhou Wang Yi Zhao Xinlan Liu Yujin Hou Wenbiao Ma Jingqi Han Xiaofeng Zhou Dengfeng Ren Fuxing Zhao Zitao Li Shifen Huang Yongzhi Chen Yingjian He Yan Liu Zijun Zhu Yongxin Li Jinming Li Mengting Da Hongnan Mo Feng Du Liang Cui Jing Bai Zhen Liu Fei Ma Jiuda Zhao Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial Signal Transduction and Targeted Therapy |
| title | Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial |
| title_full | Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial |
| title_fullStr | Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial |
| title_full_unstemmed | Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial |
| title_short | Neoadjuvant apatinib addition to sintilimab and carboplatin-taxane based chemotherapy in patients with early triple-negative breast cancer: the phase 2 NeoSAC trial |
| title_sort | neoadjuvant apatinib addition to sintilimab and carboplatin taxane based chemotherapy in patients with early triple negative breast cancer the phase 2 neosac trial |
| url | https://doi.org/10.1038/s41392-025-02137-7 |
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