Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial
| Autor: | Riikka Huovinen, Henrik Lindman, Päivi Auvinen, Pirkko-Liisa Kellokumpu-Lehtinen, Peter Canney, Judith Fraser, Oskar Johansson, Liisa Sailas, P. Halonen, Diana Ritchie, Teppo Huttunen, Meri Utriainen, Hans Wildiers, Taina Turpeenniemi-Hujanen, Paul Nyandoto, Kenneth Villman, Jeffrey Yachnin, Patrick Neven, Heikki Joensuu, Vernon Harvey, Helena Granstam-Bjorneklett, Lotta Lundgren, Minna Tanner |
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| Přispěvatelé: | Heikki Joensuu / Principal Investigator, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, University of Helsinki, HYKS erva |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Oncology
Cancer Research Time Factors Receptor ErbB-2 medicine.medical_treatment Kaplan-Meier Estimate THERAPY 0302 clinical medicine Trastuzumab Antineoplastic Combined Chemotherapy Protocols 030212 general & internal medicine skin and connective tissue diseases Original Investigation DOCETAXEL Hazard ratio NCCTG N9831 Middle Aged Chemotherapy regimen 3. Good health Docetaxel Chemotherapy Adjuvant 030220 oncology & carcinogenesis SAFETY Female medicine.drug Epirubicin medicine.medical_specialty 3122 Cancers Breast Neoplasms Drug Administration Schedule 03 medical and health sciences Breast cancer Internal medicine medicine Humans COMBINATION neoplasms Neoplasm Staging Chemotherapy Taxane business.industry JOINT ANALYSIS medicine.disease ta3122 ONCOLOGY NSABP B-31 business FOLLOW-UP Follow-Up Studies |
| Popis: | IMPORTANCE: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear. OBJECTIVE: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab. DESIGN, SETTING, AND PARTICIPANTS: Open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m2) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries. INTERVENTION: Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year. MAIN OUTCOMES AND MEASURES: The primary objective was DFS; secondary objectives included distant disease-free survival, overall survival, cardiac DFS, and safety. RESULTS: In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease-free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m2 had inferior and those treated with 100 mg/m2 had similar DFS as patients in the 1-year group. CONCLUSIONS AND RELEVANCE: Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00593697. ispartof: JAMA ONCOLOGY vol:4 issue:9 pages:1199-1206 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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