“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,” the researchers observed.
The study was a secondary analysis of randomized phase 3 multicenter clinical trial data that was conducted between Aug. 1, 1993, and July 31, 1999. The patient population was women with breast cancer aged younger than 56 years who had at least four involved axillary lymph nodes. Follow-up data from medical records, general practitioners, the Dutch national statistical office, and nationwide cancer registries were gathered between June 1, 2016, and Dec. 31, 2017. Women were randomized 1:1 to receive five cycles of either CDCT (fluorouracil, 500 mg/m2; epirubicin, 90 mg/m2; and cyclophosphamide, 500 mg/m2) or HDCT; HDCT patients received the same first four cycles as CDCT patients, and the fifth cycle was cyclophosphamide, 6000 mg/m2; thiotepa, 480 mg/m2; and carboplatin, 1600 mg/m2; followed by hematopoietic stem cell transplant. The primary outcome measures were overall survival and safety, as well as cumulative incidence risk of a second malignant neoplasm or cardiovascular events.
Mixed Survival Benefits, No Significant Long-term Risks
Final analysis included 885 women with breast cancer (mean [SD] age, 44.5 [6.6] years), of whom 442 were randomized to receive HDCT and 443 were randomized to receive CDCT; median follow-up time was 20.4 years (interquartile range, 19.2–22.0 years). During follow-up, the 20-year overall survival was higher in the HDCT group than the CDCT group (45.3% vs. 41.5%; hazard ratio [HR]=0.89; 95% confidence interval [CI], 0.75–1.06). in patients who had at least 10 involved axillary lymph nodes, the absolute improvement in 20-year overall survival was 14.6% (HR=0.72; 95% CI, 0.54–0.95), and for women with triple-negative breast cancer, 15.4% (HR=0.67; 95% CI, 0.42–1.05). There were no significant differences between the HDCT group and CDCT group in the cumulative incidence risk of a second malignant neoplasm at 20 years (12.1% vs. 16.2%; P=0.10) or major cardiovascular events; however, the HDCT group had higher rates of hypertension (21.7% vs. 14.3%, P=0.02), hypercholesterolemia (15.7% vs. 10.6%, P=0.04), and dysrhythmias (8.6% vs. 4.6%, P=0.005).
The study was published in JAMA Oncology.
“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),” the study authors concluded. “High-dose chemotherapy did not affect long-term risk of a second malignant neoplasm or major cardiovascular events.”