Trastuzumab Plus Radiotherapy Did Not Achieve Significant Reduction in Ipsilateral Breast Cancer Rates for HER2-Positive DCIS

Even though the trastuzumab/radiotherapy failed to meet the trial-specified reduction threshold, a modest, statistically nonsignificant reduction in ipsilateral breast cancer rates were observed.

In the randomized B-43 trial, adding trastuzumab (Herceptin) to radiotherapy treatment did not achieve the objective of a 36% reduction in ipsilateral breast cancer rate for women with HER2-positive ductal carcinoma in situ (DCIS), according to data published in the Journal of Clinical Oncology.

While the research failed to meet its main objective, the data did show a modest, albeit clinically nonsignificant, reduction in ipsilateral breast cancer rate of 19% for this cohort of patients.

“The combination of trastuzumab plus radiotherapy did not statistically reduce rates of ipsilateral breast cancer compared with radiotherapy alone in this prospective, randomized controlled clinical trial and did not achieve its primary aim,” wrote the investigators.

The patient population consisted of 2014 patients with HER2-positive DCIS resected by lumpectomy, with patients randomized to either the radiotherapy-alone arm or radiotherapy-plus-trastuzumab arm. The median follow-up as of December 31, 2019 was 79.2 months.

At the primary definitive analysis, 114 ipsilateral breast cancer events occurred, with 63 events in the radiotherapy arm and 51 events in the radiotherapy plus trastuzumab arm (HR, 0.81; 95% CI, 0.56-1.17; P = .26).

More specifically, 38 of the 114 events were invasive, with 18 and 20 events occurring in the radiotherapy and radiotherapy plus trastuzumab arms, respectively (HR, 1.11; 95% CI, 0.59-2.10; P = .71). Seventy-six events were DCIS, with 45 in the radiotherapy arm and 31 in the radiotherapy plus trastuzumab arm (HR, 0.68; 95% CI, 0.43-1.08; P = .11).

Overall, the research did not meet the 163 protocol-specified events defined by the study design. Because of this, the trial’s results were determined to be negative.

“It should be noted that this trial did not address the efficacy of trastuzumab in patients with HER2-positive DCIS so extensive that mastectomy was required but, rather, a population of HER2-positive patients whose disease could be resected by lumpectomy with clear margins,” wrote the investigators. “Further exploration of radiotherapy plus trastuzumab in lumpectomy candidates is needed in HER2-positive DCIS before this therapy is offered routinely.”

Eligible patients had an ECOG performance score of 0 or 1, DCIS resected by lumpectomy, known estrogen receptor and/or progesterone receptor, and HER2 status determined by centralized testing.

Whole-breast radiotherapy was given concurrently with trastuzumab. Overall, the intent-to-treat primary analysis was conducted either after 163 ipsilateral breast cancer events occurred or when all accrued patients were on the study for 5 or more years.

The research team explained that, “to our knowledge, this is the first prospective, randomized controlled clinical trial to evaluate the effectiveness of trastuzumab when added to radiotherapy in a HER2-positive patient cohort with DCIS.”


Cobleigh MA, Anderson SJ, Siziopikou KP, et al. Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial. J Clin Oncol. March 19, 2021. doi: 10.1200/JCO.20.02824