[audio mp3="https://www.audiomedica.com/wp-content/2025/07/Sarah-Tolaney-Rebecca-Dent-Giuseppe-Curigliano-ASCO-AJO-2025-PRODUCTIO-MASTER.mp3"][/audio]Speaker: Sara M Tolaney MD MPH, Chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Associate Professor of Medicine, Harvard Medical School, Boston USA
Interview:Rebecca Dent MD, Deputy Chief Executive Officer, National Cancer Center, Singapore
Interview: Giuseppe Curigliano MD PhD, Director, Early Drug Development for Innovative Therapies Division, European Institute of Oncology, University of Milan, Milan, Italy
CHICAGO, USA—Patients with HER2 positive advanced or metastatic breast cancer lived 40.7 months without relapse after being treated with a combination of the antibody drug conjugate trastuzumab deruxtecan (T-DXd) as their first line therapy. This was 13.8-month longer than with the standard of care consisting of a taxane plus trastuzumab and pertuzumab with 26.9 months with the standard of care consisting of a taxane plus trastuzumab and pertuzumab, and suggests that the ADC combination therapy could become standard. This was in interim findings from the DESTINY-Breast09 study reported at the American Society of Clinical Oncology Annual Meeting held in Chicago. The Audio Journal of Oncology heard from DESTINY study leader
Sara M Tolaney MD MPH from the Dana-Farber Cancer Institute in Boston USA. To comment on the study findings Peter Goodwin interviewed ASCO Expert
Rebecca Dent, from the National Cancer Center, Singapore
. Peter also asked
Giuseppe Curigliano MD PhD of the European Institute of Oncology and the University of Milan, Milan, Italy to describe the emerging landscape of antibody drug conjugate therapies for breast cancer.
Summary: DESTINY-Breast09 is the first trial in more than a decade to demonstrate a clinically meaningful improvement in outcomes for a broad group of patients with HER2-positive metastatic breast cancer in the first-line setting. Initial treatment with trastuzumab deruxtecan (T-DXd) plus pertuzumab delivered a 13.8-month improvement in median progression-free survival (PFS) compared with the standard regimen of a taxane plus trastuzumab and pertuzumab (THP). Plans for regulatory submission are underway while the trial continues to collect longer-term data and compare T-DXd alone versus THP. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. Initial results from the phase 3 DESTINY-Breast09 trial conducted in patients with HER2-positive advanced or metastatic breast cancer showed that first-line treatment with T-DXd plus pertuzumab extends PFS by more than 1 year when compared with THP—the current standard of care, established in the CLEOPATRA trial in 2012.1 These findings not only met the primary study endpoint at the interim analysis but also position T-DXd plus pertuzumab to become a new treatment standard (LBA1008). After a median follow-up of 29.0 months, median PFS by blinded independent central review reached 40.7 months with T-DXd plus pertuzumab versus 26.9 months with THP—a clinically meaningful improvement of 13.8 months (Figure). This difference between arms translates to a 44% reduction in the risk of disease progression or death with the T-DXd plus pertuzumab regimen (HR 0.56, 95% CI [0.44, 0.71]; P < .00001).
SARAH MAXWELL: For patients with metastatic breast cancer testing positive for HER2, there’s encouraging news about using an antibody-drug conjugate, or ADC, as
first line therapy. I’m Sarah Maxwell, with the Audio Journal of Oncology. At the 2025 Annual Meeting of the American Society of Clinical Oncology in Chicago, early findings were reported from the DESTINY-Breast 09 study. The study used the ADC trastuzumab deruxtecan, otherwise known as T-DXd—that delivers the topoisomerase 1 inhibitor deruxtecan, to HER2-expressing cancer cells. Study leader Sara Tolaney from the Dana-Farber Cancer Institute in Boston, USA:
SARAH TOLANEY: “We know that about 15 per cent ….. ……… up front has been a big area of interest.” (0’58 secs) The question Dr. Tolaney’s team investigated was: Could the ADC, alone or in combination with an anti-HER2 agent, do better than standard-of-care? In the early results reported at ASCO
, the DESTINY-Breast 09 study looked primarily at progression-free survival:
SARAH TOLANEY: “Destiny Breast 09 took patients who had previously… ……with trastuzumab plus pertuzumab.” (0:17secs) And the DESTINY-Breast 09 early results were reported in a late-breaking abstract at the 2025 ASCO conference:
SARAH TOLANEY: “The data that we’re presenting here at ASCO ….…..option for patient with metastatic HER2 positive breast cancer.” (0:59 secs) Sara Tolaney, Chief of the Division of Breast Oncology at the Dana-Farber Cancer Institute, also Associate Professor of Medicine at Harvard Medical School, in Boston, USA. At the ASCO Annual Meeting in Chicago Rebecca Dent, Deputy Chief Executive Officer of the National Cancer Centre in Singapore, was invited to comment on the DESTINY findings. Our reporter Peter Goodwin asked her to summarise her thoughts on the new data:
REBECCA DENT: “The big thing …… …………. ……And we’ll wait for longer term follow up.” (8: 16secs) Rebecca Dent, Senior Consultant Medical Oncologist and Deputy Chief Executive Officer at Singapore’s National Cancer Centre,
and Scientific Chair of the 2024 meeting of the European Society for Medica Oncology, talking with Peter Goodwin. The new findings from DESTINY-Breast 09 seem now to be adding to a growing toolbox of ADC treatments available for patients with breast cancer. To comment on the landscape for using ADCs—including T-DXd—Peter called in to see Giuseppe Curigliano, from the European Institute of Oncology and the University of Milan, in Italy.
GIUSEPPE CURIGLIANO: IN: “There’s a revolution going ….. OUT: ….. that can improve survival in metastatic breast cancer. (3:52 secs) Professor Giuseppe Curigliano, Director of the Early Drug Development for Innovative Therapies Division of the European Institute of Oncology and the University of Milan, in Italy, who, by the way, will be President of the European Society for Medical Oncology for 2027-2028. That’s all for now. You can hear more from the Audio Journal of Oncology very soon, wherever you get your favourite podcasts. Until then, from me Sarah Maxwell and the rest of the team, Good-bye!
ABSTRACT TITLE: Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09.
Background: DESTINY-Breast09 (NCT04784715) is a global, randomized Phase 3 study assessing the efficacy and safety of 1L T-DXd ± P vs THP in 1157 pts with HER2+ a/mBC. The CLEOPATRA study established THP as standard of care in this setting over a decade ago.
Methods: Eligible pts had centrally confirmed HER2+ (IHC 3+ or ISH+) a/mBC and no prior chemotherapy or HER2-directed therapy for a/mBC ([neo]adjuvant HER2-directed therapy / chemotherapy with a disease-free interval of >6 months [mo] and ≤1 line of endocrine therapy for metastatic disease permitted). Pts were randomized 1:1:1 to T-DXd 5.4 mg/kg (+ placebo), T-DXd + P, or THP, stratified by de-novo vs recurrent disease, and hormone receptor (HR) and
PIK3CA mutation status. In this planned interim analysis, data for T-DXd + P vs THP are presented; the T-DXd + placebo arm remains blinded until final PFS analysis. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in the intent-to-treat population. Other endpoints included overall survival (OS), PFS by investigator (INV), objective response rate (ORR), duration of response (DOR), and safety.
Results: Among the pts randomized to T-DXd + P (n=383) and THP (n=387), 52% had de-novo disease and 54% had HR+ status; demographic and disease characteristics were well balanced. At this interim data cutoff (Feb 26, 2025; median follow up 29 mo; 38% mature for PFS), T-DXd + P significantly improved PFS by BICR (hazard ratio 0.56; 95% CI 0.44, 0.71; P<0.00001) and INV (Table). PFS benefit was consistent across all subgroups. OS data were immature. Median response duration with T-DXd + P exceeded 3 years (Table). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 63.5% and 62.3%, and serious TEAEs in 27.0% and 25.1%, of pts in the T-DXd + P and THP groups, respectively. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 46 (12.1%; predominantly Gr 1/2; n=2 [0.5%] Gr 5) pts who received T-DXd + P, and 4 (1.0%; all Gr 1/2) who received THP.
Conclusions: T-DXd + P demonstrated a statistically significant and clinically meaningful improvement in PFS vs THP that was consistently observed across all subgroups and may represent a new 1L standard of care in HER2+ a/mBC; no new safety signals were identified. Audio Journal of Oncology, July 25 2025 Title: [caption id="attachment_4300" align="alignleft" width="240"]
Rebecca Dent MD[/caption] [caption id="attachment_4301" align="alignleft" width="240"]
Giuseppe Curigliano, MD PhD[/caption]
First-Line T-DXd Combination Adds More Than a Year of Progression Free Survival for Patients with Advanced HER2 Positive BreastCancer
