“The hypothesis had been that it would be only the HER2-amplified patients who would benefit from this.” An additional study, N9831, added to the confusion by showing similar outcomes for 156 patients whose samples were found to be HER2-low.
Severe toxicities were infrequent and no new safety signals were observed. It was not possible to explain the outcome differences among patients in the earlier, adjuvant trials. Investigators concluded that “there is no benefit with trastuzumab therapy in patients with FISH ratios <2.0 and IHC staining intensity of 1+ or 2+.”
Asked if changes in testing procedures over time may have contributed to the findings, Fehrenbacher said that, if anything, testing has gotten better, and in the case of B-47, the testing was tightened up to ensure higher quality results.
He said the results came as a surprise, particularly because of the sharpness of the demarcation between those who benefit from trastuzumab and those who do not. “Biologically, it’s hard to imagine that a FISH ratio of 2.1 gets full benefit and a FISH ratio of 1.9 gets no benefit.”
Fehrenbacher L, Cecchini RS, Geyer CE, et al. NSABP B-47 (NRG Oncology) phase III RCT comparing adjuvant chemotherapy ACweekly paclitaxel (WP) or TC x 6 with or without trastuzumab for 1 year in high-risk, invasive breast cancer, negative for HER2 by ISH and with IHC 1+ or 2+ (HER2-Low IBC). Presented at: SABCS; December 5-9, 2018; San Antonio, Texas.