Among women with human epidermal growth factor receptor 2-positive (HER2+) ductal carcinoma in situ (DCIS), the addition of trastuzumab to radiation therapy (RT) achieved a statistically insignificant 19% reduction in the rate of ipsilateral breast tumor recurrence (IBTR), according to study results published in the Journal of Clinical Oncology.
While a majority of DCIS lesions will never progress to invasive breast cancer, a proportion of patients with DCIS exhibit microinvasion and overexpression of HER2. Preclinical studies have shown that inhibition of HER2 with trastuzumab can enhance the effectiveness of radiation therapy, the study authors explained.
In the B-43 phase 3 trial (ClinicalTrials.gov Identifier: NCT00769379), researchers compared the effectiveness of RT with or without concurrent trastuzumab in patients with HER2+ DCIS post-lumpectomy. The study included 2014 participants who were randomly assigned to receive RT alone (1008 patients) or RT plus trastuzumab (1006 patients). The median follow-up duration was 79.2 months.
At primary analysis, there were 114 IBTR events, with 63 confirmed IBTR events in the RT group and 51 in the RT plus trastuzumab group (hazard ratio [HR], 0.81; 95% CI, 0.56-1.17; P =.26). Of the total 114 IBTR events, 34 were invasive (18 in the RT group and 20 in the RT plus trastuzumab group; HR, 1.11; 95% CI, 0.59-2.10; P =.71), and 76 were noninvasive (45 in the RT group and 31 in the RT plus trastuzumab group; HR, 0.68; 95% CI, 0.43-1.08; P =.11).
There were 48 deaths reported (26 in the RT group and 22 in the RT plus trastuzumab group; HR, 0.85; 95% CI, 0.48-1.51; P =.59). In addition, there were 150 confirmed second primary cancers (78 in the RT group and 72 in the RT plus trastuzumab group; HR, 0.91; 95% CI, 0.66-1.25; P =.57) and 4 distant recurrences (1 in the RT group and 3 in the RT plus trastuzumab group).
The trial did not achieve the objective of a 36% reduction in the IBTR rate.
“In summary, although NSABP B-43 did not meet its primary [endpoint] and had negative results, the trial did show that the addition of [trastuzumab] to RT was safe and, although not statistically significant, results were associated with a 19% reduction in IBTRs (the rate of which has decreased over time), a 17% reduction in recurrences, and a 16% reduction in all [DCIS-free survival] events,” the authors reported.
“Further exploration of RT plus [trastuzumab] in lumpectomy candidates is needed in [HER2+] DCIS before this therapy is offered routinely,” they added.
Disclosure: This research was supported by Genentech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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. Published online March 19, 2021. doi:10.1200/JCO.20.02824