Enhertu OK ends 10-year EU gap in frontline breast cancer

AstraZeneca and Daiichi Sankyo's Enhertu, given in combination with Roche's Perjeta, has become the first new frontline therapy for unresectable or metastatic HER2-positive breast cancer in the EU for over a decade.

Enhertu (trastuzumab deruxtecan) and Perjeta (pertuzumab) have been approved by the European Commission for the new indication on the strength of the DESTINY-Breast09 study, a highlight of the 2025 ASCO cancer congress.

Compared to the standard first-line regimen of trastuzumab, pertuzumab and taxane chemotherapy known as THP, Enhertu/Perjeta achieved a statistically significant 44% reduction in the risk of disease recurrence or death, extending median progression-free survival (PFS) from 26.9 months to 40.7 months.

There was also a trend towards improved overall survival with Enhertu/Perjeta that will be watched closely, with further patient follow-up.

"For patients diagnosed with HER2-positive metastatic breast cancer, maintaining disease control for as long as possible in the first-line setting is a critical treatment goal," said study investigator Cristina Saura of Vall d'Hebron University Hospital in Barcelona, Spain.

Enhertu plus Perjeta "has the potential to become the new first-line standard of care," she added.

DESTINY-Breast09 is also comparing Enhertu monotherapy with THP in another arm of the 1,157-patient study, but the data for that hasn't been unblinded yet.

Daiichi and AZ already have approval for this frontline indication in the US, which came in towards the end of last year, and the frontline indication is a key element in their objective of driving brand north of $5.4 billion in global sales this year.

"This approval brings Enhertu to patients in the EU earlier in the course of their metastatic disease and sets a new benchmark for…PFS in the first-line setting," commented Dave Fredrickson, head of AZ's oncology and haematology business unit.

Frontline use is also viewed as a stepping stone towards even earlier use of Enhertu in neoadjuvant and adjuvant settings, stemming from the DESTINY-Breast11 and DESTINY-Breast05 studies.

The ADC is already approved in the US and under regulatory review in the EU for patients with HER2-positive breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment, based on the DESTINY-Breast05 results.