High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes: 20-Year Follow-up of a Phase 3 Randomized Clinical Trial.

Autor:	Steenbruggen TG; Department of Medical Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands., Steggink LC; Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands., Seynaeve CM; Department of Medical Oncology, Erasmus MC University Medical Center, Rotterdam, the Netherlands., van der Hoeven JJM; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands., Hooning MJ; Department of Medical Oncology, Erasmus MC University Medical Center, Rotterdam, the Netherlands., Jager A; Department of Medical Oncology, Erasmus MC University Medical Center, Rotterdam, the Netherlands., Konings IR; Department of Medical Oncology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands., Kroep JR; Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands., Smit WM; Department of Internal Medicine/Medical Oncology, Medisch Spectrum Twente, Enschede, the Netherlands., Tjan-Heijnen VCG; Department of Medical Oncology, Maastricht University Medical Center, Maastricht, the Netherlands., van der Wall E; Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands., Bins AD; Department of Medical Oncology, Amsterdam UMC, location AMC, Amsterdam, the Netherlands., Linn SC; Department of Medical Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands., Schaapveld M; Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands., Jacobse JN; Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands., van Leeuwen FE; Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands., Schröder CP; Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands., van Tinteren H; Department of Biostatistics, the Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands., de Vries EGE; Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands., Sonke GS; Department of Medical Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands., Gietema JA; Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2020 Apr 01; Vol. 6 (4), pp. 528-534.
DOI:	10.1001/jamaoncol.2019.6276
Abstrakt:	Importance: Trials of adjuvant high-dose chemotherapy (HDCT) have failed to show a survival benefit in unselected patients with breast cancer, but long-term follow-up is lacking. Objective: To determine 20-year efficacy and safety outcomes of a large trial of adjuvant HDCT vs conventional-dose chemotherapy (CDCT) for patients with stage III breast cancer. Design, Setting, and Participants: This secondary analysis used data from a randomized phase 3 multicenter clinical trial of 885 women younger than 56 years with breast cancer and 4 or more involved axillary lymph nodes conducted from August 1, 1993, to July 31, 1999. Additional follow-up data were collected between June 1, 2016, and December 31, 2017, from medical records, general practitioners, the Dutch national statistical office, and nationwide cancer registries. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from February 1, 2018, to October 14, 2019. Interventions: Participants were randomized 1:1 to receive 5 cycles of CDCT consisting of fluorouracil, 500 mg/m2, epirubicin, 90 mg/m2, and cyclophosphamide, 500 mg/m2, or HDCT in which the first 4 cycles were identical to CDCT and the fifth cycle was replaced by cyclophosphamide, 6000 mg/m2, thiotepa, 480 mg/m2, and carboplatin, 1600 mg/m2, followed by hematopoietic stem cell transplant. Main Outcomes and Measures: Main end points were overall survival and safety and cumulative incidence risk of a second malignant neoplasm or cardiovascular events. Results: Of the 885 women in the study (mean [SD] age, 44.5 [6.6] years), 442 were randomized to receive HDCT, and 443 were randomized to receive CDCT. With 20.4 years median follow-up (interquartile range, 19.2-22.0 years), the 20-year overall survival was 45.3% with HDCT and 41.5% with CDCT (hazard ratio, 0.89; 95% CI, 0.75-1.06). The absolute improvement in 20-year overall survival was 14.6% (hazard ratio, 0.72; 95% CI, 0.54-0.95) for patients with 10 or more invoved axillary lymph nodes and 15.4% (hazard ratio, 0.67; 95% CI, 0.42-1.05) for patients with triple-negative breast cancer. The cumulative incidence risk of a second malignant neoplasm at 20 years or major cardiovascular events was similar in both treatment groups (20-year cumulative incidence risk for second malignant neoplasm was 12.1% in the HDCT group vs 16.2% in the CDCT group, P = .10), although patients in the HDCT group more often had hypertension (21.7% vs 14.3%, P = .02), hypercholesterolemia (15.7% vs 10.6%, P = .04), and dysrhythmias (8.6% vs 4.6%, P = .005). Conclusions and Relevance: High-dose chemotherapy provided no long-term survival benefit in unselected patients with stage III breast cancer but did provide improved overall survival in very high-risk patients (ie, with ≥10 involved axillary lymph nodes). High-dose chemotherapy did not affect long-term risk of a second malignant neoplasm or major cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT03087409.
Databáze:	MEDLINE
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