'Clinically Meaningful' Response for Presurgical T-DM1 in HER2+ HR+ Early Breast Cancer

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Neoadjuvant therapy with the antibody-drug conjugate trastuzumab emtansine (T-DM1) offers clinical response rates in 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.”

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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.

Reference

  1. 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.

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.”

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.

Reference

1.     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, T

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