The emergence of positive data from trials like PATINA creates a dilemma for oncologists treating patients who are already stable on an older maintenance therapy. The consensus suggests not altering a successful regimen to avoid disrupting patient stability, revealing a cautious approach to integrating new evidence into established care.

The HER2CLIMB-02 trial found that adding tucatinib to TDM-1 offered only a modest 2-month PFS benefit. This came at the cost of substantially increased toxicity, including transaminitis and diarrhea, suggesting the two agents are better used sequentially for most patients.

Despite compelling data from trials like PATINA, some patients with ER+/HER2+ breast cancer refuse maintenance endocrine therapy due to side effects. This highlights a real-world gap between clinical trial evidence and patient adherence, forcing oncologists to navigate patient preferences against optimal treatment protocols.

Due to cumulative toxicity concerns with TDXD, particularly ILD, clinicians express more comfort with the shorter 4-cycle neoadjuvant course from DESTINY-Breast11 than the prolonged 14-cycle adjuvant therapy in DESTINY-Breast05, favoring front-loading the treatment.

Data from DESTINY-Breast09 shows TDXD plus pertuzumab dramatically improved progression-free survival in first-line metastatic HER2+ breast cancer. This unprecedented efficacy raises new questions about optimal treatment duration and the potential for de-escalated maintenance therapy after induction.

A patient's time to progression on first-line CDK4/6 inhibitor therapy acts as an informal biomarker. A shorter duration, such as 14 months, is viewed by experts as "not so great" and indicates a degree of underlying endocrine resistance that influences subsequent treatment strategies.

The DESTINY-Breast11 trial showed a neoadjuvant regimen of TDXD followed by THP achieved a 67.3% pathologic complete response (pCR) rate in high-risk HER2+ breast cancer. This is the highest pCR rate seen in a registrational trial, signaling a potential new standard of care.

In metastatic breast cancer, approximately one-third of patients are unable to proceed to a second line of therapy due to disease progression or declining performance status. This high attrition rate argues for using the most effective agents, such as ADCs, in the first-line setting.

A subtle finding in the DESTINY-Breast11 trial, where TDXD alone underperformed TDXD followed by THP, suggests that taxane-based chemotherapy might remain effective even after a patient's HER2-positive cancer becomes resistant to the antibody-drug conjugate TDXD.