CHMP Backs Enhertu+Pertuzumab in 1L HER2+ mBC

Key Takeaways

• CHMP recommended Enhertu plus pertuzumab for first-line unresectable or metastatic HER2-positive breast cancer on 23 July 2026.
• DESTINY-Breast09 reported HR 0.56 for PFS vs THP; median PFS 40.7 vs 26.9 months.
• Confirmed ORR was 85.1% vs 78.6%; median DOR 39.2 vs 26.4 months, per Daiichi Sankyo.
• ILD/pneumonitis occurred in 12.1% on the combination arm, including two grade 5 events (0.5%).

Enhertu plus pertuzumab at a glance

Field	Detail
Product	Enhertu (trastuzumab deruxtecan) + pertuzumab
Sponsors	Daiichi Sankyo; AstraZeneca
Regulator action	CHMP positive opinion (23 July 2026)
Proposed use	1L unresectable/metastatic HER2-positive breast cancer
Key trial	DESTINY-Breast09 (NCT04784715)
Key efficacy	PFS HR 0.56; median PFS 40.7 vs 26.9 months
Next step	European Commission decision

What did CHMP decide?

EMA's variation page states that on 23 July 2026 CHMP adopted a positive opinion recommending Enhertu in combination with pertuzumab for first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer. The opinion still requires a European Commission decision before the label change is authorised across the EU.

Primary sources: EMA's Enhertu variation opinion and EMA's July 2026 CHMP meeting highlights.

What did DESTINY-Breast09 show?

Daiichi Sankyo said Enhertu plus pertuzumab reduced the risk of disease progression or death by 44% versus taxane, trastuzumab and pertuzumab (THP) (HR 0.56; 95% CI 0.44–0.71; p<0.00001). Median PFS by BICR was 40.7 months versus 26.9 months. Confirmed ORR was 85.1% versus 78.6%, with more complete responses on the Enhertu arm (15.1% vs 8.5%). Median duration of response was 39.2 versus 26.4 months.

Trial registration: ClinicalTrials.gov NCT04784715. Peer-reviewed readout: NEJM DESTINY-Breast09 publication.

How does safety look so far?

Sponsors said the combination safety profile matched known individual-drug risks, with no new signals. In 381 treated patients, the most common grade ≥3 treatment-related events included neutropenia (23.9%), hypokalemia (10.2%) and anemia (8.4%). Independent adjudication found ILD or pneumonitis in 12.1%, mostly grade 1–2, with two grade 5 events (0.5%).

Company detail: Daiichi Sankyo's 24 July 2026 Enhertu CHMP release (PDF).

Why does first-line HER2-positive disease still need new options?

THP has been the EU first-line standard for more than a decade, yet many patients progress within about two years and roughly one in three never reach later lines after first-line failure, according to sponsor epidemiology notes. A CHMP-backed regimen with median PFS beyond three years would be the first major EU first-line shift in that setting if the Commission concurs.

What should clinicians watch next?

• Final SmPC wording on biomarker testing (IHC/ISH) and prior adjuvant washout rules
• ILD monitoring requirements and dose-modification language
• How payers sequence Enhertu-pertuzumab versus THP and later-line Enhertu monotherapy
• The still-blinded Enhertu monotherapy arm of DESTINY-Breast09 and the DESTINY-Breast05 residual-disease review

A positive CHMP opinion is not yet a marketing authorisation. National pricing and hospital formulary decisions will determine real-world timing after any Commission approval.

What remains uncertain?

Overall survival maturity, long-term ILD rates outside trial centres, and HTA rankings versus THP are still open. Cross-trial comparisons with other ADCs remain inappropriate until head-to-head or real-world evidence accumulates.

Related NovaPharma coverage

• CHMP July 2026: 12 New Medicines Recommended
• EMA Backs Etcamah for ESR1+ Breast Cancer
• ESMO 2026 Preview: Madrid Oncology Catalysts

Frequently Asked Questions

Primary Sources

1. EMA: Enhertu variation opinion — 23 July 2026
2. Daiichi Sankyo: Enhertu plus pertuzumab CHMP opinion PDF — 24 July 2026
3. ClinicalTrials.gov: DESTINY-Breast09 NCT04784715
4. NEJM: DESTINY-Breast09 publication