Neoadjuvant TDM-1 was shown to be effective in treating HER2-positive, HR-positive breast cancer compared with trastuzumab, with or without endocrine therapy.
Results from a phase II trial showed that neoadjuvant TDM-1 is effective in treating HER2-positive, hormone receptor (HR)-positive breast cancer, with or without endocrine therapy, in comparison with trastuzumab and endocrine therapy. Results of the study (abstract 506) were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.
The WSG-ADAPT trial is an umbrella trial that included around 5,000 patients. This sub-study of that trial included patients with HER2-positive, HR-positive early breast cancer; it enrolled 376 patients at 48 sites, and this interim analysis included 130 of those patients. The trial has been closed early because efficacy was reached.
The patients were randomized to receive either TDM-1 monotherapy (37 patients), TDM-1 with endocrine therapy (48 patients), or trastuzumab with endocrine therapy (45 patients). “This was not a low-risk population,” said study presenter Nadia Harbeck, MD, PhD, of the University of Munich, noting that over half of the patients were premenopausal and about half had tumors that were larger than 2 cm.
The rate of pathologic complete response (pCR), defined as no invasive tumor in breast and nodes, was 40.5% with TDM-1 alone, 45.8% with TDM-1 and endocrine therapy, and only 6.7% with trastuzumab and endocrine therapy (P < .001 for both TDM-1 groups vs trastuzumab). Harbeck said that these pCR rates “compare quite well to other trials in this subpopulation.”
Interestingly, the results with TDM-1 differed by menopausal status. Significantly more postmenopausal women received benefit with the use of TDM-1 monotherapy compared with premenopausal women; when endocrine therapy was added, there was no difference.
There was low overall toxicity, with only seven grade 3 adverse events related to study medications; all patients recovered completely.
“I think it’s not unreasonable to state that our trial shows that therapy de-escalation is possible,” Harbeck said. “And I think this is a route we should pursue for the benefit of our patients.”
Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, the discussant for the session, called the results “striking.” She added that it is of interest that there was only minimal improvement with the addition of endocrine therapy to TDM-1. Harbeck stressed that these results are only an interim analysis, and that the full data set will provide a clearer picture.