breast cancer

Comparison of Radiation with or without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma in situ Resected by Lumpectomy: A Phase III Clinical Trial

In the July 20, 2021 edition of Journal of Clinical Oncology, Melody Cobleigh and colleagues report on the results of a phase III trial of radiation with or without concurrent trastuzumab for Her2 positive ductal carcinoma in situ.


The primary aim of the B-43 study was to evaluate the utility and efficacy of radiotherapy alone vs concurrent radiotherapy plus trastuzumab in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS).


Patient with an ECOG of 0-1, DCIS resected via lumpectomy, with documented ER, PR and HER-2/neu status were included for evaluation. Whole-breast radiotherapy was given concurrently with trastuzumab, with stratification by menopausal status, adjuvant endocrine therapy, and nuclear grade. Definitive intent-to-treat primary analysis was conducted when either 163 IBTR events occurred or all the accrued participants were on the study 5 years or longer.


2,014 participants were randomly assigned, with a median follow-up time of 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm n= 63 and RT plus T arm n= 51 (HR, 0.81; 95% CI, 0.56 – 1.17; p = .26). There were 34 who were invasive: RT arm n= 18 and RT + T arm, 20 (HR, 1.11; 95% CI, 0.59 – 2.10; p= .71). 76 were DCIS: RT arm n= 45 and RT plus T arm n= 31 (HR, 0.68; 95% CI, 0.43 – 1.08; p= .11). Annual IBTR event rates were: RT arm, 0.99%/year and RT + T arm, 0.79%/year.  Since the 163 protocol-specified events never occurred, the definitive analysis was triggered by the ≥ 5 year event.


The authors concluded”

Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.”