The addition of trastuzumab to adjuvant chemotherapy did not improve outcomes for patients with HER2-low invasive breast cancer, according to the results of the phase 3 NSABP B-47 trial published in the Journal of Clinical Oncology.
Post hoc subset analyses of previous large randomized clinical trials suggested patients with non-HER2–overexpressing disease may benefit from the addition of trastuzumab to adjuvant chemotherapy, providing rationale to conduct the NSABP B-47 trial.
The NSABP B-47 trial randomly assigned 3270 women with HER2-low invasive breast cancer to receive adjuvant chemotherapy alone or adjuvant chemotherapy followed by 1 year of trastuzumab. Patients were eligible if they had an immunohistochemistry (IHC) score of 1+ or 2+ with fluorescence in situ hybridization (FISH) ratio of less than 2.0 or a HER2 gene copy number of less than 4. Patients were followed for a median of 46 months.
Patients who received trastuzumab in addition to chemotherapy did not have a lower likelihood of invasive disease recurrence (hazard ratio [HR], 0.98; 95% CI, 0.76 to 1.25; P =.85) compared with patients who received only chemotherapy. The estimated 5-year invasive disease-free survival (IDFS) rates were also similar between the treatment groups (89.8% chemotherapy with trastuzumab vs 89.2% chemotherapy alone).
A lack of IDFS benefit from trastuzumab was seen across subgroups, including level of HER2 IHC expression (ie, 1+ or 2+), lymph node involvement, and hormone-receptor status.
Patients who received trastuzumab in addition to chemotherapy also did not have an improved distant recurrence-free interval (HR=1.10; 95% CI, 0.81 – 1.50; P = .55) or overall survival (HR=1.33; 95% CI, 0.90 – 1.95; P = .15) compared with patients who received only chemotherapy.
“Trastuzumab does not benefit women without IHC 3+ or FISH ratio-amplified breast cancer,” the study authors concluded.
Disclosure: Some of the authors disclosed financial relationships with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the original study.
Fehrenbacher L, Cecchini RS, Geyer CE Jr, et al. NSABP B-47/NRG oncology phase III randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER2 by FISH and with IHC 1+ or 2 [published online December 10, 2019]. J Clin Oncol. doi: 10.1200/JCO.19.01455