Establishing the Modern Second-Line Standard in HER2-Positive Breast Cancer

In this opening segment, panelists discuss sequential treatment strategies in HER2-positive breast cancer, emphasizing how emerging evidence is rapidly reshaping clinical practice. The session’s goal is to synthesize recent clinical trial data and translate it into practical guidance for treatment sequencing across disease stages.

Panelists describe current evidence-based approaches to second-line therapy in metastatic HER2-positive breast cancer. Dr. VK Gadi discusses the highly fluid treatment landscape, with advances occurring not only in the metastatic setting but also earlier in neoadjuvant and adjuvant care, creating downstream implications for sequencing. Within this evolving context, he emphasizes that trastuzumab deruxtecan (T-DXd) has clearly established itself as the preferred second-line option for patients who have not previously received it.

Dr. Gadi cites head-to-head trial data demonstrating superior efficacy of T-DXd compared with T-DM1, acknowledging that this benefit comes with important safety considerations. However, he stresses that with appropriate monitoring and proactive toxicity management, these risks are manageable and should not preclude use in appropriate patients. He also notes that patient expectations have shifted, with many now anticipating access to this highly effective therapy.

Alternative regimens remain relevant in select clinical scenarios. T-DM1 may still be appropriate for patients with poor performance status or significant comorbidities, whereas tucatinib-containing regimens, such as the HER2CLIMB combination, are particularly attractive for patients with known or suspected brain metastases due to their central nervous system (CNS) activity. Despite these nuances, Dr. Gadi concludes decisively that, in the absence of contraindications, T-DXd currently represents the clear standard answer for second-line therapy in HER2-positive metastatic breast cancer.