In a French-Belgian phase III trial (ASTER 70s) reported in The Lancet, Brain et al examined the survival benefit of adding adjuvant chemotherapy to hormone therapy in women aged ≥ 70 years with estrogen receptor–positive, HER2-negative breast cancer with high-risk disease on the basis of genomic grade index (GGI).
Study Details
In the multicenter trial, 1,089 women with a GGI high-risk tumor were randomly assigned between April 2012 and April 2016 to receive four cycles of adjuvant taxane- or anthracycline-based chemotherapy given every 3 weeks followed by hormone therapy (chemotherapy group, n = 541) or hormone therapy alone (control group, n = 548). Chemotherapy consisted of three options: doxorubicin, nonpegylated liposomal doxorubicin, or docetaxel, each combined with cyclophosphamide. Hormone therapy consisted of tamoxifen, an aromatase inhibitor, or a sequence of the two for 5 years. Patients had a median age of 75.1 years (interquartile range = 72.5–78.7 years). The primary endpoint was overall survival.
Key Findings
Median follow-up was 7.8 years (95% confidence interval [CI] = 7.5–7.8 years).
Overall survival rates were 90.5% (95% CI = 87.6%–92.8%) in the chemotherapy group vs 89.3% (95% CI = 86.2%–91.6%) in the control group at 4 years, and 72.7% (95% CI = 67.8%–77.0%) in the chemotherapy group vs 68.3% (95% CI = 63.3%–72.7%) in the control group at 8 years (hazard ratio = 0.83, 95% CI = 0.63–1.11, P = .2100). Statistically nonsignificant absolute differences in survival probability were observed at both 4 years (1.3%, 95% CI = –2.4% to 5.0%) and 8 years (4.5%, 95% CI = –2.1% to 11.1%).
Grade ≥ 3 adverse events occurred in 34% of patients in the chemotherapy group vs 9% of those in the control group. Events in the chemotherapy group were primarily hematological, gastrointestinal, skin, or administration site–related events or infections. Adverse events led to discontinuation of treatment in 7% of the chemotherapy group. One treatment-related death was observed in the chemotherapy group, due to peritonitis.
The investigators concluded: “The addition of adjuvant chemotherapy to [hormone therapy] conferred no survival benefit in women aged 70 years and above with a GGI high-risk estrogen receptor–positive HER2-negative breast cancer, and was associated with more adverse events, providing important data on the benefit–risk balance of adding adjuvant chemotherapy to adjuvant [hormone therapy] in this older age group.”
Etienne Brain, MD, Department of Medical Oncology, Institut Curie, Saint-Cloud, France, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Programme Hospitalier de Recherche Clinique, Cephalon, Amgen, Ipsogen, Ligue Contre le Cancer, and others. For full disclosures of all study authors, visit thelancet.com.
