'Clinically Meaningful' Response for Presurgical T-DM1 in HER2+ HR+ Early Breast Cancer
Neoadjuvant therapy with the antibody-drug conjugate trastuzumab emtansine (T-DM1) offers clinical response rates in breast cancer.
SAN ANTONIO—Neoadjuvant therapy with the antibody-drug conjugate trastuzumab emtansine (T-DM1) with or without endocrine therapy (ET) offers clinical response rates without systemic chemotherapy in HER2-positive, hormone receptor (HR)-positive early breast cancer, according to findings from a phase 2 trial that were presented at the 2015 San Antonio Breast Cancer Symposium.1
“More than 40% pCR (breast and nodes) was seen in T-DM1-treated patients after 12 weeks without systemic therapy,” reported lead author Nadia Harbeck, MD, of the Breast Center, University of Munich, in Germany. “Adding endocrine therapy to T-DM1 does not increase pCR,” irrespective of patients' menopausal status.”
“Therapy de-escalation in HER2-positive/HR-positive early breast cancer is possible,” she concluded.
T-DM1 and T-DM1 with ET achieved 41% and 41.5% pCR, respectively, and trastuzumab with ET was associated with a 15.1% pCR, Dr Harbeck reported.
Early tumor response, defined as low cellularity or Ki67 drop 30% or higher, was associated with increased pCR. “Early tumor response predicts pCR and can already be detected after 3 weeks,” she noted.
The researchers found overall toxicity to be very low and no new safety signals. A total of 18 serious adverse events (SAE) related to therapy were recorded, 5 of which were grade 3 or higher (2 in the T-DM1 group; 3 with T with ET). There were no therapy-related deaths.
The Women's Healthcare Study Group-Adjuvant Dynamic marker-Adjusted Personalized Therapy (WSG-ADAPT) HER2+/HR+ trial is the first large prospective, randomized phase 2 study “specifically conducted within this distinct subtype,” Dr Harbeck said.
“In HER2-positive early breast cancer pCR rates after standard neoadjuvant chemotherapy and anti-HER2 therapy differ according to hormone-receptor (HR) status,” Dr Harbeck noted. “Molecular analysis reveals HER2-positive/HR-positive breast cancer as a distinct entity within HER2-positive breast cancer. The ADAPT HER2-positive/HR-positive phase 2 trial aims to identify early responders to endocrine plus anti-HER2 therapy.”
RELATED: Fusion Breast Tumor Recurrence Risk, Genomic Instability
A total of 376 women were enrolled. Inclusion criteria included confirmed ER-positive and/or PR-positive and HER2-positive breast cancer, confirmed by central pathology, clinical T1c-T4a-c, no distant metastasis, adequate organ function, and normal left-ventricular ejection and electrocardiogram.
Additional clinical trials are needed to separately investigate therapy approaches to HER2-positive/HR-positive and HER2-positive/HR-negative breast cancer. “Ongoing biomarker analyses include further mutation analysis and intrinsic subtypes in the total trial collective,” Dr Harbeck concluded.
- Harbeck N, Gluz O, Christgen M, et al. Final analysis of WSG-ADAPT HER2+/HR+ phase II trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant TDM1 with or without endocrine therapy versus trastuzumab+endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer. Oral presentation at: San Antonio Breast Cancer Symposium 2015; December 11, 2015; San Antonio, TX.