Enhertu+Pertuzumab CHMP: 44% Risk Cut in HER2 Breast Cancer

The EMA’s CHMP recommended approval of Enhertu (trastuzumab deruxtecan) plus pertuzumab as first-line treatment for adults with unresectable or metastatic HER2-positive breast cancer on July 24, 2026. The positive opinion moves the regimen closer to EU approval roughly seven months after the FDA cleared the same combination on December 15, 2025.

AstraZeneca (AZN) closed at $169.26 on July 24, with a market cap near $263 billion. Daiichi Sankyo, co-developer and ADR ticker DSNPY, trades OTC with limited US volume. The CHMP opinion is a revenue expansion event, not a stock-moving catalyst for a mega-cap, but it locks in EU market access for this regimen.

What the data showed

The recommendation is based on the Phase 3 DESTINY-Breast09 trial, which randomized 1,157 patients 1:1:1 to Enhertu monotherapy, Enhertu plus pertuzumab, or the current standard of care THP (taxane, trastuzumab, pertuzumab). The primary endpoint was progression-free survival by blinded independent central review.

The combination arm delivered a 44% reduction in the risk of disease progression or death versus THP (hazard ratio 0.56, 95% CI 0.44 to 0.71, p<0.00001). Median PFS was 40.7 months with Enhertu plus pertuzumab compared to 26.9 months with THP. That is nearly 14 additional months of median progression-free survival in the first-line setting, a margin that essentially closes the debate over which regimen oncologists should start with.

The trial was presented at the 2025 ASCO Annual Meeting and published in The New England Journal of Medicine.

Why this matters

Enhertu is a HER2-directed antibody-drug conjugate: a trastuzumab antibody linked to a topoisomerase I inhibitor payload (DXd) via a cleavable peptide linker. The ADC binds HER2 on the tumor cell, is internalized, and releases the cytotoxic payload inside the cell. The “bystander effect,” where released payload diffuses to neighboring tumor cells regardless of HER2 expression, is what gives Enhertu activity even in HER2-low disease.

HER2-positive breast cancer accounts for 15% to 20% of metastatic cases. The standard first-line regimen for over a decade has been THP. A 40.7-month median PFS in first-line metastatic disease is a result that redefines expectations for this patient population, where median survival historically ranged from 18 to 24 months on older regimens.

The safety profile in DESTINY-Breast09 was consistent with the known profiles of each drug, with no new safety signals. Interstitial lung disease and pneumonitis remain the key risks for Enhertu, with grade 1-2 ILD incidence around 11.6% in earlier trials. Oncologists manage this with active monitoring and dose holds, but it constrains use.

Competitive context

The EU approval expands Enhertu’s reach into a market where it already competes with Roche’s Kadcyla and the older trastuzumab-based regimens. The Trodelvy plus Keytruda CHMP opinion in first-line TNBC, covered separately, shows how the ADC class is moving earlier in the treatment sequence across breast cancer subtypes.

What to watch

The European Commission typically follows CHMP within 67 days, so EU approval should land by late September. Watch for pricing and reimbursement negotiations in Germany and the UK, which often gate real-world uptake. The AstraZeneca press release and Daiichi Sankyo release are the primary sources.

The risk factor: Enhertu’s ILD safety signal limits how aggressively oncologists can combine it with other agents, and EU reimbursement timelines can stretch well beyond the EC decision.