Dr Tiwari on Optimal Treatment Sequencing in HER2+ Breast Cancer

Shruti Tiwari, MD, medical oncologist, Virginia Cancer Specialists, discusses optimal treatment sequencing within the realm of HER2-positive breast cancer, highlighting how to treat these patients when they present with central nervous system (CNS) involvement.

In the realm of HER2-positive breast cancer management, navigating decision-making regarding newer treatments poses a significant challenge for oncologists, Tiwari begins. The crux of the matter lies in determining the optimal sequence of these treatments, a conundrum that currently lacks a definitive answer, she explains. The dynamic nature of medical advancements means that studies evaluating treatment efficacy are conducted within the framework of existing standards of care, which inevitably evolve with the approvals of novel drugs, according to Tiwari. Consequently, the pressing issue becomes how to effectively sequence these medications, a task growing increasingly complex across various subtypes of breast cancer, including HER2-positive, triple-negative, and hormone receptor–positive disease, Tiwari elucidates.

A pertinent question arises regarding the selection between a tucatinib (Tukysa)–based regimen and fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with HER2-positive breast cancer with CNS involvement, she expands. Drawing upon the findings from the phase 2 HER2CLIMB study (NCT02614794), which investigated the efficacy of trastuzumab plus capecitabine (Xeloda) and tucatinib in patients with HER2-positive metastatic breast cancer, it is evident that this regimen generates commendable efficacy in managing CNS disease, Tiwari says. Notably, a considerable sum of patients with brain metastases exhibited no requirement for additional treatment at the 1-year mark, Tiwari reports.

Navigating CNS metastases within the context of breast cancer treatment presents challenges, as systemic therapies often fall short in controlling disease progression, necessitating frequent surgical interventions and other therapeutic modalities, she continues. Thus, the 24.1% 1-year progression-free survival rate observed among patients with brain metastases in this trial underscores the promise of the HER2CLIMB regimen as a frontline treatment approach, Tiwari emphasizes. Although preliminary data exist regarding the use of trastuzumab deruxtecan in this patient population, comprehensive insights are pending the completion of ongoing trials, such as the phase 1b/2 DESTINY-Breast07 trial (NCT04538742), Tiwari says. Until then, the HER2CLIMB regimen remains a preferred choice in clinical practice, Tiwari concludes.