Dr. Gogineni on De-Escalation Strategies in HER2+ Breast Cancer

Keerthi Gogineni, MD, MSHP, an assistant professor in the Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, discusses de-escalation strategies in HER2-positive breast cancer.

The phase III KRISTINE study, presented at the 2019 ASCO Annual Meeting by Sara Hurvitz, MD, looked at women who had larger stage II/III HER2-positive tumors. Investigators assessed whether ado-trastuzumab emtansine (T-DM1; Kadcyla) could be used in combination with pertuzumab (Perjeta) rather than the more toxic regimen composed of docetaxel/carboplatin/trastuzumab (Herceptin) plus pertuzumab (TCHP), without sacrificing efficacy.

The combination showed a lower rate of grade 3 toxicity than TCHP. However, event-free survival (EFS) appeared to be inferior in the T-DM1/pertuzumab arm. It looked like the inferior EFS was mostly driven by early progressors, which shed light on who is more likely to respond to the combination.

The patients who didn't progress before surgery were strongly HER2-positive, says Gogineni; these patients did well with TCHP. Furthermore, the rates of invasive disease-free survival are virtually inseparable. This presents a potential option for de-escalation for larger HER2-positive tumors, adds Gogineni. However, careful consideration of HER2 heterogeneity and HER2 expression will be necessary to ensure that the right population is being selected for de-escalated approaches.