ENHERTU, a HER2-directed antibody-drug conjugate already approved in over 85 countries as a second-line treatment, could become a first-line option, potentially setting a new standard of care for this aggressive cancer.

While adverse events were common, with 99.7% experiencing treatment-emergent issues, the safety profile remained consistent with known effects, and no new safety concerns emerged.

Serious adverse events included interstitial lung disease and cardiotoxicity, with some cases of fatal ILD reported, highlighting the importance of monitoring during treatment.

The combination therapy also nearly doubled the number of patients with no evidence of disease on imaging, increasing complete responses from 33 to 58.

HER2-positive metastatic breast cancer affects 15-20% of metastatic cases, with around 10,000 patients treated annually in the US in the first-line setting, and current treatments have struggled to significantly extend progression-free survival.

T-DXd, the antibody-drug conjugate used in the combination, targets HER2-positive cancer cells and delivers a topoisomerase I inhibitor payload designed to minimize systemic toxicity, with multiple approvals for various HER2-expressing cancers.

The promising trial results suggest that ENHERTU plus pertuzumab could soon become a new standard of care, offering hope for improved outcomes in a challenging patient population.

Despite the high incidence of adverse events, the safety profile of the combination remains consistent with known effects of the individual drugs, emphasizing the importance of careful management during treatment.

Common severe adverse effects included neutropenia, hypokalemia, anemia, and ILD, with some cases of fatal ILD, underscoring the need for vigilant safety monitoring.

The trial's success in nearly doubling complete response rates highlights the potential of this combination to significantly improve disease eradication in HER2-positive metastatic breast cancer.

The FDA has granted Priority Review to ENHERTU combined with pertuzumab for HER2-positive metastatic breast cancer, following positive phase 3 trial results from DESTINY-Breast09 that showed a 44% reduction in disease progression or death and a median progression-free survival exceeding three years.

The trial reported an impressive overall response rate of 85.1%, with 15.1% of patients achieving complete responses, nearly doubling the response rate seen with standard therapy.