The addition of trastuzumab to radiotherapy did not reach the protocol objective of a 36% reduction in the ipsilateral breast tumor recurrence rate for women with HER2-positive ductal carcinoma in situ (DCIS) in the NRG Oncology clinical trial NSABP B-43. The trial did find a modest (19%) reduction in the rate of recurrence among women who received trastuzumab, but this difference was not statistically significant. These findings were presented by Cobleigh et al during the ASCO20 Virtual Scientific Program (Abstract 508).
Study Details
The phase III trial accrued 2,014 women and randomly assigned trial participants in a 1:1 fashion to receive either whole-breast radiotherapy alone or radiotherapy with two doses of trastuzumab following lumpectomy. The goal of the trial was to determine if the addition of trastuzumab can assist in preventing recurrence of ipsilateral breast cancer, ipsilateral skin cancer, ipsilateral DCIS, or ipsilateral breast tumor recurrence in women with DCIS. This hypothesis was developed in response to data from previous preclinical studies suggesting that trastuzumab may boost the effectiveness of radiotherapy.
Of the 2,014 patients that were accrued to the trial, 1,998 patients (99.2%) had follow-up information available at the median follow-up time point of 79.2 months. About 2,000 women had radiotherapy information available; 98.2% of patients completed radiotherapy treatment in the radiotherapy-alone arm and 98.1% completed radiotherapy in the radiotherapy-plus-trastuzumab arm. In the radiotherapy-plus-trastuzumab group, 94.3% patients completed both doses of trastuzumab therapy, whereas 2.5% had only one dose of the therapy. Another 3.2% did not start trastuzumab.
The NRG Oncology/NSABP B-43 protocol required that 163 in-breast tumor recurrence events be confirmed or that all patients be on study for at least 5 years to trigger a definitive analysis. Since fewer than 163 in-breast tumor recurrence events were confirmed, analysis was performed because all patients were on the trial for 5 years or longer.
Results
“This is the first prospective, randomized study of HER2-targeted treatment for HER2-positive DCIS. It provides important insight into the natural history and impact of HER2-targeted treatment on outcomes.”— Melody Cobleigh, MD
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At this preliminary analysis based on information through December 31, 2019, 114 in-breast tumor recurrence events were confirmed, with 63 in the radiotherapy-alone arm and 51 in the radiotherapy-plus-trastuzumab arm. Among recurrences, 38 were invasive, including 18 in the radiotherapy arm and 20 in the radiotherapy-plus-trastuzumab arm. The remaining 76 in-breast tumor recurrence events were DCIS, with 45 in the radiotherapy treatment arm and 31 in the radiotherapy-plus-trastuzumab arm.
Annual in-breast tumor recurrence event rates were 0.99% per year in the radiotherapy group and 0.80% per year in the radiotherapy-plus-trastuzumab group. There were 48 deaths on the trial, with 26 in the radiotherapy-alone arm and 22 in the radiotherapy-plus-trastuzumab arm.
“This is the first prospective, randomized study of HER2-targeted treatment for HER2-positive DCIS. It provides important insight into the natural history and impact of HER2-targeted treatment on outcomes,” stated lead author Melody Cobleigh, MD, of Rush University Medical Center, in a statement.
Disclosure: This study was supported by the National Cancer Institute and Genentech. For full disclosures of the study authors, visit coi.asco.org.
