NEOADJUVANT TDM1 IN HER2+ BREAST CANCER

A West German Study Group phase II trial, reported by Harbeck et al in the Journal of Clinical Oncology, has shown a higher pathologic complete response rate with neoadjuvant ado-trastuzumab emtansine (formerly known as T-DM1; Kadcyla) with or without endocrine therapy vs trastuzumab (Herceptin) with endocrine therapy in early HER2-positive, hormone receptor–positive breast cancer.

Study Details

In the ADAPT study, 375 patients from 48 German sites were randomized 1:1:1 between October 2012 and March 2015 to receive ado-trastuzumab emtansine at 3.6 mg/kg every 3 weeks for 4 cycles with (n = 127) or without (n = 119) endocrine therapy or trastuzumab at a loading dose of 8 mg/kg followed by 6 mg/kg every 3 weeks for 3 more cycles plus endocrine therapy (n = 129). Recommended endocrine therapy was tamoxifen in premenopausal women and aromatase inhibitors in postmenopausal women.

The primary endpoint was pathologic complete response (ypT0/is/ypN0) after 12 weeks. Early response was defined as proliferation decrease ≥ 30% Ki67 or cellularity response using core biopsies at week 3 during treatment.

Pathologic Complete Response Rate

Overall, pathologic complete response was observed in 41.0% of patients in the ado-trastuzumab emtansine group and 41.5% of the ado-trastuzumab emtansine plus endocrine therapy group vs 15.1% of the trastuzumab plus endocrine therapy group (P < .001 for both comparisons). Among 304 patients assessable for early response, 203 (67.1%) were considered early responders.

Pathologic complete response was achieved in 35.7% of early responders vs 19.8% of those without early response (odds ratio = 2.2, 95% confidence interval = 1.24–4.19). Pathologic complete response rates for early responders vs non-early responders in each treatment group were 39.3% vs 25.0%, 47.4% vs 24.0%, and 17.7% vs 12.5%.

Adverse Events

Ado-trastuzumab emtansine was associated with a significantly higher rate of grade 1 and 2 adverse events, particularly thrombocytopenia, nausea, and elevated liver enzymes. Grade ≥ 3 adverse events occurred in 7.5% of ado-trastuzumab emtansine patients vs 4.1% of trastuzumab patients. Treatment-related serious adverse events occurred in 5.3% vs 3.1%.

The investigators concluded: “The ADAPT HER2-positive/[hormone receptor–]positive trial demonstrates that neoadjuvant [ado-trastuzumab emtansine] (with or without [endocrine therapy) given for only 12 weeks results in a clinically meaningful [pathologic complete response] rate. Thus, a substantial number of patients are spared the adverse effects of systemic chemotherapy.

The study was supported by Hoffmann la Roche.

Nadia Harbeck, MD, of the University of Munich, is the corresponding author of the Journal of Clinical Oncology article.