SAN ANTONIO – Treating high-risk breast cancer patients who tested low for HER2-receptor status with trastuzumab (Herceptin) provided no benefit in disease-free survival over women who are treated only with chemotherapy, researchers reported here.
The 5-year overall invasive disease-free survival was 89.2% of women treated with chemotherapy alone compared with disease free survival of 89.6% in the women who were given chemotherapy and trastuzumab (P=0.90), reported Louis Fehrenbacher, MD, of Kaiser Permanente Northern California in Vallejo.
“We observed an overall survival of 95% in both arms of the trial,” he told MedPage Today at the 2017 San Antonio Breast Cancer Symposium.
Invasive disease events occurred in 134 women receiving just chemotherapy and 130 women getting chemotherapy plus trastuzumab during the 5 years of the study, Fehrenbacher reported at an SABCS press conference.
The trial was prompted by a finding in the 2005 National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 study. Its main finding was an advantage for trastuzumab in women with HER2-receptor overexpression, but it also found a possible advantage in a small subset of women who were apparently misidentified as having overexpression but actually had low HER2 levels. Fehrenbacher and colleagues wanted to confirm whether this was real or some sort of fluke.
Apparently it was the latter.
“We usually don’t present studies with negative findings but these results are very important because we have many patients who are 1+ and 2+ and we have been wondering if we should be giving them a fairly expensive drug with side effect for a full year,” said Virginia Kaklamani, MD, of UT Health at San Antonio.
Why the current study – designated as NSABP B-47 – did not confirm the earlier result is not readily explained, Fehrenbacher said. He speculated that, in the earlier study, the HER2-low cases might actually have been HER2-positive. The findings in the original trial showed a trend toward benefit in the small group of patients, but those findings did not reach statistical significance.
To pursue the possible use of HER2-targeted agents in this expanded community of HER2-low breast cancer, Fehrenbacher and colleagues enrolled 3,270 women who were identified as having HER2-low breast cancer by immunohistochemistry (1+, 2+) — a level that would not normally be treated with trastuzumab.
They received chemotherapy at the choice of their provider, either doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 in four cycles every 3 weeks followed by 12 weeks of once-weekly paclitaxel; or docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks for six cycles. The chemotherapy alone was randomly provided to 1,603 women; the chemotherapy plus trastuzumab was given to 1,599 women. There were 63 patients (1.9%) lost to follow-up.
“This will probably reduce the amount of trastuzumab being used, although it shouldn’t,” Fehrenbacher said. “There were probably a few cases in which the women had low or near HER2 levels but not quite the 3+ required. I think that the number of these patients being treated with trastuzumab is pretty low at the moment, but that number should go to zero. There was no benefit and there was toxicity, it is time consuming and it is expensive.”
He said that there were no statistically significant differences when looking at stratification by level of HER2-low status; by the number of positive lymph nodes; by hormone receptor status; or by type of chemotherapy. “There were no trends for efficacy observed,” he said.
Fehrenbacher said that the high survival was somewhat of a surprise: “These patients did extremely well. If you look at studies of outcomes over 30 years you see that there is an incremental improvement in the same stages of cancer decade after decade. Whether that is due to more lower stage diagnosis, less risk within the same stage, or maybe the treatment is better, the organization is better in providing care … it is hard to know why but it is very clear that outcomes in each stage are improving.”
Fehrenbacher disclosed relevant relationships with Genentech/Roche, CellDex, Abbvie, Macrogenitcs, Cascadian and Pfizer.
Kaklamani disclosed relevant relationships with Novartis and Pfizer.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner