Adding trastuzumab to standard adjuvant chemotherapy does not improve survival or reduce recurrence in patients with early-stage breast cancer expressing low levels of HER2, according to results of a National Surgical Adjuvant Breast and Bowel Project study reported at the 2017 San Antonio Breast Cancer Symposium (SABCS).

In the prospective phase III NSABP B-47 study, 3,270 patients with node-positive or high-risk node-negative invasive breast cancer with low HER2 expression (immunohistochemistry [IHC] score of 1+ or 2+ with fluorescence in situ hybridization [FISH] ratio <2.0) were randomized to receive standard adjuvant chemotherapy with or without 1 year of trastuzumab. The patients were followed for a median of 46.1 months. [SABCS 2017, abstract GS1-02]

At 5 years, the primary endpoint of invasive disease-free survival (IDFS) did not differ significantly between the trastuzumab and chemotherapy arms (89.6 vs 89.2 percent; hazard ratio [HR], 0.98; p=0.90).

“Further analysis showed no significant difference in IDFS between the two groups when patients were stratified by level of HER2 IHC expression, level of lymph node involvement, hormone receptor status, or the chemotherapy regimen chosen,” reported investigator Dr Louis Fehrenbacher of Kaiser Permanente Oncology Vallejo Medical Center, California, US.

“Secondary endpoints also did not differ significantly between the two groups,” he said. “There were no trends for efficacy with adding trastuzumab to adjuvant chemotherapy.”

The 5-year point estimate for recurrence-free interval (RFI) was 92 percent for the trastuzumab group vs 92.2 percent for the chemotherapy group (HR, 0.995; p=0.91), while the 5-year estimate for distant recurrence-free interval (DRFI) was 92.7 vs 93.5 percent (HR, 1.10; p=0.55).

“The addition of trastuzumab did not significantly improve overall survival [OS]. The 5-year point estimate for OS was 94.8 percent in the trastuzumab group vs 96.2 percent in the chemotherapy group [HR, 1.33; p=0.14],” said Fehrenbacher.

“We were surprised at the results, which contradict findings of two previous landmark studies [NSABP B-31 and N9831] showing benefit of adding trastuzumab to adjuvant chemotherapy in patients with HER2-low breast cancer,” he continued. “A likely explanation for the difference in findings is tumour heterogeneity between the locally and centrally tested tumour samples in the previous studies.”

In the NSABP B-47 study, 4.3 percent of patients in the trastuzumab group and 5 percent of those in the chemotherapy group experienced grade 4/5 toxicities. Chemotherapy (docetaxel and cyclophosphamide every 3 weeks for six cycles, or doxorubicin and cyclophosphamide every 2 or 3 weeks for four cycles followed by paclitaxel every week for 12 cycles) was chosen by participating physicians. Docetaxel/cyclophosphamide was the intended regimen for 44.2 percent of the patients.

“Patients in both treatment groups did quite well in our study,” said Fehrenbacher. “NSABP B-47 did not confirm the retrospective findings of NSABP B-31 and N9831. The threshold of HER2 expression or genetic amplification for trastuzumab benefit remains unchanged.”