As reported in the Journal of Clinical Oncology by Nadia Harbeck, MD, PhD, and colleagues, 5-year follow-up from the phase II WSG-ADAPT-TP trial indicated that pathologic complete response (pCR) was associated with better outcomes irrespective of receipt of adjuvant chemotherapy among patients with hormone receptor–positive, HER2-positive early breast cancer receiving de-escalated neoadjuvant ado-trastuzumab emtansine (T-DM1) with or without endocrine therapy (ET) vs trastuzumab plus ET.
Nadia Harbeck, MD, PhD
Study Details
In the trial, 375 patients were randomly assigned 1:1:1 to 12 weeks of T-DM1 with no ET (T-DM1 group), T-DM1 plus ET, or trastuzumab plus ET, with T-DM1 and trastuzumab given once every 3 weeks. Adjuvant chemotherapy could be omitted in patients with pCR and was mandatory in patients without pCR. As previously reported, pCR rates were higher with T-DM1 with (41.5%) and without ET (41%) compared with trastuzumab plus ET (15.1%). The current analysis included 117 patients in the T-DM1 group, 120 in the T-DM1 plus ET group, and 120 in the trastuzumab plus ET group who received at least one dose of study treatment.
Key Findings
The T-DM1, T-DM1 plus ET, and trastuzumab plus ET groups had similar 5-year invasive disease-free survival rates (88.9%, 85.3%, and 84.6%, overall P = .608) and overall survival rates (97.2%, 96.4%, and 96.3%, overall P = .534).
Among a total of 117 patients with pCR vs patients without pCR, 5-year invasive disease–free survival was 92.7% vs 82.7% (hazard ratio [HR] = 0.40; 95% confidence interval [CI] = 0.18–0.85); 5-year overall survival was also significantly improved with pCR vs no PCR (HR = 0.36, 95% CI = 0.10–1.23).
Among the 117 patients with pCR, 41 did not receive adjuvant chemotherapy; 5-year invasive disease–free survival was 93.0% (95% CI = 84.0%–97.0%) among those who did not receive adjuvant chemotherapy vs 92.1% (95% CI = 77.5%–97.4%) among those who received adjuvant chemotherapy (P = .848).
Exploratory translational analysis indicated that factors associated with better outcomes among all patients included PIK3CA wild-type tumors, high immune marker expression, and luminal-A tumors (by PAM50).
The investigators concluded, “The WSG-ADAPT-TP trial demonstrated that pCR after 12 weeks of chemotherapy-free de-escalated neoadjuvant therapy was associated with excellent survival in [hormone receptor–]positive/HER2-positive early breast cancer without further adjuvant chemotherapy. Despite higher pCR rates for T-DM1 with or without ET vs trastuzumab plus ET, all trial arms had similar outcomes because of mandatory standard chemotherapy after non-pCR. WSG-ADAPT-TP demonstrated that such de-escalation trials in HER2-positive early breast cancer are feasible and safe for patients. Patient selection on the basis of biomarkers or molecular subtypes may increase the efficacy of systemic chemotherapy-free HER2-targeted approaches.”
Dr. Harbeck, of Department of Gynecology and Obstetrics and CCCMunich, Breast Center, LMU University Hospital, Munich, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by F. Hoffmann-La Roche Ltd. For full disclosures of the study authors, visit ascopubs.org.
