M Graeser, O Gluz, C Zu Eulenburg, S Kuemmel, R von Schumann, M Christgen, R Wuerstlein, E Pelz, H H Kreipe, P Schmid, M Thill, M Braun, J Potenberg, C Schumacher, J Tio, J Schumacher, L Wujak, A D Hartkopf, M Just, C Schem, K Luedtke-Heckenkamp, F Hilpert, A Kentsch, R E Kates, U Nitz, N Harbeck
{"title":"HER2+早期乳腺癌降级新辅助治疗后的生存预测：三个WSG试验的汇总分析","authors":"M Graeser, O Gluz, C Zu Eulenburg, S Kuemmel, R von Schumann, M Christgen, R Wuerstlein, E Pelz, H H Kreipe, P Schmid, M Thill, M Braun, J Potenberg, C Schumacher, J Tio, J Schumacher, L Wujak, A D Hartkopf, M Just, C Schem, K Luedtke-Heckenkamp, F Hilpert, A Kentsch, R E Kates, U Nitz, N Harbeck","doi":"10.1016/j.annonc.2025.07.016","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>We analyzed outcomes and survival predictors in three West German Study Group (WSG) randomized de-escalation trials (ADAPT-HR-/HER2+, ADAPT-TP, TP-II) in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC) investigating short (12-week) neoadjuvant treatments with or without chemotherapy.</p><p><strong>Patients and methods: </strong>A total of 713 patients were analyzed; neoadjuvant chemotherapy (paclitaxel plus pertuzumab plus trastuzumab): n = 149, neoadjuvant chemotherapy-free (pertuzumab plus trastuzumab, trastuzumab-only)/antibody-drug conjugate (ADC, trastuzumab emtansine) treatment: n = 564. Patients with pathological complete response (pCR, ypT0/is ypN0) were allowed to omit further chemotherapy; chemotherapy was mandatory after non-pCR. The primary endpoint of each trial was pCR; survival was the secondary endpoint. Survival was analyzed using the Kaplan-Meier method and Cox regression.</p><p><strong>Results: </strong>Median follow-up was 60.7 months. In total, 10 (7%) and 74 (13%) invasive disease-free survival (iDFS) events, 8 (5%) and 51 (9%) distant DFS (dDFS) events, and 6 (4%) and 34 (6%) deaths occurred in the neoadjuvant chemotherapy and chemotherapy-free/ADC groups, respectively; the respective 5-year survival rates were 96% [95% confidence interval (CI) 92% to 99%] and 88% (95% CI 85% to 91%) for iDFS (hazard ratio 0.56, 95% CI 0.29-1.08, P = 0.083) and 98% (95% CI 93% to 99%) and 97% (95% CI 95% to 98%) for overall survival (hazard ratio 0.88, 95% CI 0.36-2.11, P = 0.775). The 5-year iDFS rates in patients with pCR were 98% (95% CI 91% to 99%) after chemotherapy and 94% (95% CI 89% to 97%) after chemotherapy-free/ADC treatment (hazard ratio 0.76, 95% CI 0.27-2.12, P = 0.609). iDFS was comparable between patients with and without adjuvant chemotherapy after pCR to chemotherapy-free/ADC treatment (hazard ratio 1.25, 95% CI 0.39-4.00, P = 0.712). In multivariable analysis, node-negative status and pCR were favorably associated with iDFS in the chemotherapy-free/ADC group.</p><p><strong>Conclusions: </strong>This pooled analysis demonstrates that neoadjuvant de-escalation trials with further pCR-adapted treatment (de-)escalation are feasible and appear safe for HER2-positive eBC patients. Twelve-weekly neoadjuvant paclitaxel plus HER2 blockade is effective and well tolerated. Neoadjuvant chemotherapy-free/ADC treatments can be viable alternatives for stage I-II eBC. Excellent survival after pCR to neoadjuvant chemotherapy-free/ADC treatment lays the groundwork for further de-escalation strategies.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4000,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prediction of survival after de-escalated neoadjuvant therapy in HER2-positive early breast cancer: a pooled analysis of three WSG trials.\",\"authors\":\"M Graeser, O Gluz, C Zu Eulenburg, S Kuemmel, R von Schumann, M Christgen, R Wuerstlein, E Pelz, H H Kreipe, P Schmid, M Thill, M Braun, J Potenberg, C Schumacher, J Tio, J Schumacher, L Wujak, A D Hartkopf, M Just, C Schem, K Luedtke-Heckenkamp, F Hilpert, A Kentsch, R E Kates, U Nitz, N Harbeck\",\"doi\":\"10.1016/j.annonc.2025.07.016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>We analyzed outcomes and survival predictors in three West German Study Group (WSG) randomized de-escalation trials (ADAPT-HR-/HER2+, ADAPT-TP, TP-II) in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC) investigating short (12-week) neoadjuvant treatments with or without chemotherapy.</p><p><strong>Patients and methods: </strong>A total of 713 patients were analyzed; neoadjuvant chemotherapy (paclitaxel plus pertuzumab plus trastuzumab): n = 149, neoadjuvant chemotherapy-free (pertuzumab plus trastuzumab, trastuzumab-only)/antibody-drug conjugate (ADC, trastuzumab emtansine) treatment: n = 564. Patients with pathological complete response (pCR, ypT0/is ypN0) were allowed to omit further chemotherapy; chemotherapy was mandatory after non-pCR. The primary endpoint of each trial was pCR; survival was the secondary endpoint. Survival was analyzed using the Kaplan-Meier method and Cox regression.</p><p><strong>Results: </strong>Median follow-up was 60.7 months. In total, 10 (7%) and 74 (13%) invasive disease-free survival (iDFS) events, 8 (5%) and 51 (9%) distant DFS (dDFS) events, and 6 (4%) and 34 (6%) deaths occurred in the neoadjuvant chemotherapy and chemotherapy-free/ADC groups, respectively; the respective 5-year survival rates were 96% [95% confidence interval (CI) 92% to 99%] and 88% (95% CI 85% to 91%) for iDFS (hazard ratio 0.56, 95% CI 0.29-1.08, P = 0.083) and 98% (95% CI 93% to 99%) and 97% (95% CI 95% to 98%) for overall survival (hazard ratio 0.88, 95% CI 0.36-2.11, P = 0.775). The 5-year iDFS rates in patients with pCR were 98% (95% CI 91% to 99%) after chemotherapy and 94% (95% CI 89% to 97%) after chemotherapy-free/ADC treatment (hazard ratio 0.76, 95% CI 0.27-2.12, P = 0.609). iDFS was comparable between patients with and without adjuvant chemotherapy after pCR to chemotherapy-free/ADC treatment (hazard ratio 1.25, 95% CI 0.39-4.00, P = 0.712). In multivariable analysis, node-negative status and pCR were favorably associated with iDFS in the chemotherapy-free/ADC group.</p><p><strong>Conclusions: </strong>This pooled analysis demonstrates that neoadjuvant de-escalation trials with further pCR-adapted treatment (de-)escalation are feasible and appear safe for HER2-positive eBC patients. Twelve-weekly neoadjuvant paclitaxel plus HER2 blockade is effective and well tolerated. Neoadjuvant chemotherapy-free/ADC treatments can be viable alternatives for stage I-II eBC. Excellent survival after pCR to neoadjuvant chemotherapy-free/ADC treatment lays the groundwork for further de-escalation strategies.</p>\",\"PeriodicalId\":8000,\"journal\":{\"name\":\"Annals of Oncology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":65.4000,\"publicationDate\":\"2025-08-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.annonc.2025.07.016\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.annonc.2025.07.016","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Prediction of survival after de-escalated neoadjuvant therapy in HER2-positive early breast cancer: a pooled analysis of three WSG trials.
Background: We analyzed outcomes and survival predictors in three West German Study Group (WSG) randomized de-escalation trials (ADAPT-HR-/HER2+, ADAPT-TP, TP-II) in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC) investigating short (12-week) neoadjuvant treatments with or without chemotherapy.
Patients and methods: A total of 713 patients were analyzed; neoadjuvant chemotherapy (paclitaxel plus pertuzumab plus trastuzumab): n = 149, neoadjuvant chemotherapy-free (pertuzumab plus trastuzumab, trastuzumab-only)/antibody-drug conjugate (ADC, trastuzumab emtansine) treatment: n = 564. Patients with pathological complete response (pCR, ypT0/is ypN0) were allowed to omit further chemotherapy; chemotherapy was mandatory after non-pCR. The primary endpoint of each trial was pCR; survival was the secondary endpoint. Survival was analyzed using the Kaplan-Meier method and Cox regression.
Results: Median follow-up was 60.7 months. In total, 10 (7%) and 74 (13%) invasive disease-free survival (iDFS) events, 8 (5%) and 51 (9%) distant DFS (dDFS) events, and 6 (4%) and 34 (6%) deaths occurred in the neoadjuvant chemotherapy and chemotherapy-free/ADC groups, respectively; the respective 5-year survival rates were 96% [95% confidence interval (CI) 92% to 99%] and 88% (95% CI 85% to 91%) for iDFS (hazard ratio 0.56, 95% CI 0.29-1.08, P = 0.083) and 98% (95% CI 93% to 99%) and 97% (95% CI 95% to 98%) for overall survival (hazard ratio 0.88, 95% CI 0.36-2.11, P = 0.775). The 5-year iDFS rates in patients with pCR were 98% (95% CI 91% to 99%) after chemotherapy and 94% (95% CI 89% to 97%) after chemotherapy-free/ADC treatment (hazard ratio 0.76, 95% CI 0.27-2.12, P = 0.609). iDFS was comparable between patients with and without adjuvant chemotherapy after pCR to chemotherapy-free/ADC treatment (hazard ratio 1.25, 95% CI 0.39-4.00, P = 0.712). In multivariable analysis, node-negative status and pCR were favorably associated with iDFS in the chemotherapy-free/ADC group.
Conclusions: This pooled analysis demonstrates that neoadjuvant de-escalation trials with further pCR-adapted treatment (de-)escalation are feasible and appear safe for HER2-positive eBC patients. Twelve-weekly neoadjuvant paclitaxel plus HER2 blockade is effective and well tolerated. Neoadjuvant chemotherapy-free/ADC treatments can be viable alternatives for stage I-II eBC. Excellent survival after pCR to neoadjuvant chemotherapy-free/ADC treatment lays the groundwork for further de-escalation strategies.
期刊介绍：
Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine.
The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings.
Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.
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