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DESTINY-Breast09 — Trastuzumab deruxtecan (T-DXd) + pertuzumab, 1L HER2+ advanced/metastatic breast cancer (response-durability exploratory analysis)

Abstract: 1021 · Session: Breast Cancer—Metastatic, 2026 ASCO Annual Meeting · Presenter: Yeon Hee Park, MD, PhD (Samsung Medical Center, Seoul) · Embargo: per ASCO meeting embargo

At a glance

  • Sponsor: AstraZeneca / Daiichi Sankyo
  • PI / presenter: Yeon Hee Park, MD, PhD (Samsung Medical Center)
  • NCT ID: NCT04784715
  • Phase: 3 (this report = exploratory post hoc analysis by best confirmed response)
  • Design: Randomized, open-label, 3-arm; this analysis pools the T-DXd + pertuzumab arm and stratifies outcomes by best confirmed response (CR vs PR vs SD/PD)
  • N: ~1,157 randomized overall (T-DXd + pertuzumab vs T-DXd monotherapy vs THP); analysis within the T-DXd + pertuzumab arm
  • Primary endpoint(s): PFS by blinded independent central review (parent trial); this analysis reports duration of response (DOR), PFS, treatment duration, and safety by response subgroup
  • Comparator: Taxane + trastuzumab + pertuzumab (THP) — parent-trial control
  • Indication: HER2-positive locally advanced or metastatic breast cancer
  • Line: First-line (1L)

Headline result

In this ASCO 2026 exploratory analysis of the T-DXd + pertuzumab arm, durable complete and partial responses translated into markedly prolonged disease control. Median treatment duration was 28.0 months in patients achieving CR and 22.2 months in those achieving PR, versus 4.4 months in patients with SD/PD. Median duration of response was 39.2 months (CR) vs 26.4 months (PR). The parent DESTINY-Breast09 trial (ASCO 2025 plenary; NEJM) established the regimen's benefit: median PFS 40.7 months with T-DXd + pertuzumab vs 26.9 months with THP, HR 0.56 (44% reduction in risk of progression or death). The analysis supports that achieving CR/PR with T-DXd + pertuzumab is associated with extended treatment benefit in the 1L setting.

Mechanism / class

T-DXd (Enhertu) is a HER2-directed antibody–drug conjugate pairing trastuzumab with a topoisomerase I inhibitor payload (deruxtecan) via a cleavable linker, with bystander effect. Pertuzumab is a HER2 dimerization-inhibiting monoclonal antibody. T-DXd + pertuzumab received US approval in December 2025 for 1L HER2-positive advanced/metastatic breast cancer on the strength of DESTINY-Breast09.

Practice-changing?

Pending/confirmatory. The parent DESTINY-Breast09 result is already practice-changing and underpinned the December 2025 US approval, establishing T-DXd + pertuzumab as a new 1L benchmark. This exploratory response-durability analysis is supportive/descriptive — it reinforces the durability narrative and informs prognostic discussion but does not itself change practice.

Safety

Safety findings were consistent with the known profiles of T-DXd and pertuzumab. Rates of interstitial lung disease (ILD) / pneumonitis were similar across the CR, PR, and SD/PD response groups.

  • Other ASCO 2026 trials: see breast-cancer trials in this directory (./)
  • AACR 2026: ../../aacr-2026/index.md
  • JPM 2026: ../../jpm-2026/index.md (AstraZeneca / Daiichi Sankyo oncology pipeline)

Sources

  • ASCO Meeting Library: https://meetings.asco.org/abstracts-presentations/253126
  • ASCO Daily News: https://dailynews.ascopubs.org/do/destiny-breast09-trastuzumab-deruxtecan-plus-pertuzumab-sets-new-first-line-benchmark
  • DocWire News (ASCO 2026 coverage): https://www.docwirenews.com/post/asco-2026-durable-complete-and-partial-responses-observed-with-t-dxd-plus-pertuzumab-in-destiny-breast09
  • Parent trial (NEJM): https://www.nejm.org/doi/full/10.1056/NEJMoa2508668
  • ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT04784715