Dr Agrawal on First-Line Treatment Approaches in HER2+ Breast Cancer

Laila S. Agrawal, MD, breast medical oncologist, Medical Oncology, Norton Healthcare, discusses the primary approaches for treating patients with metastatic HER2-positive breast cancer, and highlights the continued exploration of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) for this patient population.

In advanced HER2-positive breast cancer , the initial approach to treatment commonly involves the administration of a taxane alongside trastuzumab (Herceptin) and pertuzumab (Perjeta), Agrawal begins. As patients progress in the first-line setting, an array of agents become available for consideration in second-line treatment, she states. When evaluating second-line options in the metastatic setting, tucatinib (Tukysa) plus trastuzumab and capecitabine (Xeloda) emerges as a preferred choice for many patients due to tucatinib’s efficacy and tolerability profile, she states.

Although tucatinib can confer substantial therapeutic benefit for these patients, it's important to consider the impact of potential adverse effects. Noteworthy among these is interstitial lung disease, or pneumonitis, which may require additional intervention to manage, she emphasizes.

Another notable agent in the second-line treatment armamentarium is T-DXd. The emergence of this agent has altered treatment approaches for patients with metastatic HER2-positive breast cancer, including those with HER2-low metastatic disease, Agrawal says. The agent’s versatility extends beyond the metastatic setting, with its ongoing exploration in the neoadjuvant setting. Furthermore, it has demonstrated activity in patients who exhibit residual disease following neoadjuvant chemotherapy and HER2-directed therapy, she explains. The increasing body of evidence supporting the use of T-DXd in later therapeutic lines has generated interest in itsutility as a first-line treatment option, Agrawal states.

The agent’s continued incorporation into multiple treatment lines may complicate the sequencing of therapies in HER2-positive breast cancer, Agrawal speculates. The decision-making process can also be nuanced for individuals who may have derived benefit from earlier administration of T-DXd in the neoadjuvant or adjuvant settings, especially if they have residual disease, Overall, the evolving landscape of HER2-positive breast cancer treatment underscores the ongoing exploration for personalized and effective therapeutic strategies, Agarwal concludes.