Personalized Treatments for HER2+ Breast Cancer

At the virtual 2021 Great Debates & Updates in Women’s Oncology meeting, Shanu Modi, MD, HER2 Breast Program Breast Medicine Service Memorial Sloan Kettering Cancer Center New York, provided insight on personalized treatments for patients with HER2 positive breast cancer.

Dr Modi’s presentation highlighted the key studies from the past year, starting with the lower-risk patients and working up to those at higher risk.

“For the early-stage setting, the focus has really continued to be in decelerating or escalating therapy in an attempt to personalize treatment for the individual treatment,” she explained.

Beginning with stage I HER2-positive breast cancer, Dr Modi discusses the ATEMPT trial, which included  497 patients with stage I HER2-positive breast cancer. Patients were randomized to either the APT regimen of TH (paclitaxel 80 mg/m² and trastuzumab 2 mg/kg IV weekly x12, trastuzumab 6 mg/kg every 3 weeks x13) or adjuvant T-DM1 (3.6 mg/kg IV q3 weeks x17).

The primary end points were to evaluate 3-year disease-free survival (DFS) in the T-DM1 arm and compare the incidence of clinically relevant toxicities (CRT) between the 2 arms.

The T-DM1 arm received a 97.7% three-year DFS rate (95% CI:96.2-99.3) and relapse-free interval (RFI) 99.1% (95% CI, 98.1-100). Furthermore, there were no differences in the overall rates of toxicity between the two arms. However, Dr Modi noted that further evaluation of shorter duration therapy with T-DM1 followed by trastuzumab should be considered.

In regards to higher-risk stage II HER2-positive breast cancer treatment, Dr Modi points out that achieving pathologic complete response (pCR) improves survival outcomes in HER2-positive breast cancer patients. This has led to neoadjuvant therapy becoming the preferred approach, with a focus on achieving pCR. 

The current standard for tumors greater than 2cm or with positive nodes, is to include polychemotherapy with dual HER2 blockade pertuzumab and trastuzumab, which has led to a doubling of pCR.

With higher risk patients, there is a focus on eliminating anthracyclines, in addition to scaling back on chemotherapy. Dr Modi turns to the BCIRG006, where the 10.3-year follow-up shows similar overall survival (OS) and DFS data for the non-anthracycline arm versus the anthracycline chemotherapy arm plus trastuzumab.

A similar outcome was demonstrated in the TRAIN 2 trial, which compared stage II and III HER2-positive breast cancer patients receiving neoadjuvant with an anthracycline-taxane combo and dual blockade, versus a non-anthracycline-taxane carboplatin combo plus dual blockade. The results from the TRAIN 2 trial showed near-identical pCR rates and no difference in 3-year (event-free survival) EFS and OS.
 
“We have data now from 2 large, early-stage trials, showing similar findings that suggest in the era of HER2-targeted therapies non-anthracycline chemo is a standard of care,” concluded Dr. Modi.—Alexandra Graziano