Dr Nanda on Treatment De-Escalation in HER2+ Breast Cancer and TNBC

Rita Nanda, MD, associate professor, medicine, director, Breast Oncology Program, University of Chicago Medicine, discusses the importance of neoadjuvant therapy for patients with HER2-positive breast cancer and triple-negative breast cancer (TNBC), as well as efforts to de-escalate treatment in the adjuvant setting.

Neoadjuvant therapy is the current standard of care for patients with stage II and III HER2-positive breast cancer and TNBC, Nanda begins. All patients with these disease stages should be offered neoadjuvant therapy, as their response to treatment in this setting informs the optimal selection of adjuvant approaches, Nanda says. Furthermore, clinical trials are evaluating the de-escalation of adjuvant therapy for patients who respond to neoadjuvant therapy.

For instance, the ongoing phase 2 ATEMPT 2.0 trial (NCT04893109) is assessing the use of adjuvant ado-trastuzumab emtansine (T-DM1; Kadcyla) followed by subcutaneous trastuzumab (Herceptin) vs paclitaxel plus subcutaneous trastuzumab in patients with newly diagnosed, stage I HER2-positive invasive breast cancer. To be eligible for trial enrollment, patients must be at least 18 years of age, have node-negative or micrometastatic breast cancer, and have an ECOG performance status of 0 or 1. Patients with bilateral breast cancers, multifocal disease, or multicentric disease are permitted to enroll onto the study provided that each individual tumor meets eligibility criteria. All tumors are required to be removed via modified radical mastectomy or a segmental mastectomy, with either an axillary dissection or sentinel lymph node biopsy.

Patients in the investigative arm will be randomly assigned to receive T-DM1 every 3 weeks for 6 cycles followed by trastuzumab every 3 weeks for 11 cycles. Patients in the control arm will receive paclitaxel for 4 cycles and trastuzumab every 3 weeks for 17 cycles, with the first 4 doses of each drug given concurrently. The trial’s primary end points are the incidence of clinically relevant toxicities and disease-free survival. Key secondary end points include safety, quality of life assessments, and overall survival.

Additional clinical trials are investigating novel adjuvant therapies that may reduce recurrence risk for patients who do not achieve a pathologic complete response with neoadjuvant therapy, Nanda concludes.