DESTINY-Breast09 is a Phase 3 trial of first-line trastuzumab deruxtecan (T-DXd, Enhertu) plus pertuzumab versus the standard taxane + trastuzumab + pertuzumab (THP) regimen in HER2-positive metastatic breast cancer. The T-DXd combination improved median PFS to 40.7 vs 26.9 months (HR 0.56; p<0.0001), supporting FDA approval on December 15, 2025. Sponsor: Daiichi Sankyo / AstraZeneca.
Discover KOL Sentiment on DESTINY-Breast09 →Posts by physicians about DESTINY-Breast09 during ESMO 2026 (October 2026), newest first. Each post is shown in full and verbatim and linked to the original on X.
Physician posts on the exploratory brain-metastases analysis Cristina Saura presented at ESMO 2026, newest first. Each post is shown in full and verbatim and linked to the original on X. The figures are in the brain-metastases result block.
𝕏📌 A DESTINY-Breast09 analysis of T-DXd + pertuzumab vs taxane + trastuzumab + pertuzumab for pts with HER2+ a/mBC and baseline brain metastases 🧠 ✨Cristina Saura Manich #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF https://t.co/omeRvpUWXf
𝕏#ESMO26 | DB-09 | BM efficacy We already knew T-DXd had strong intracranial activity. Here are the first-line data: in HER2+ breast cancer with BM, T-DXd+pertuzumab vs THP delivered a median PFS of 36.5 vs 11.1 mo and 12-m CNS-PFS of 88.9% vs 42.5%. Nearly double the intracranial response rate!
𝕏Oral abstract #BreastCancer session at #ESMO26: presented by super @CristinaSaura3 additional impressive data from DESTINYbreast09 on efficacy of first-line anti-HER2 #TrastuzumabDeruxtecan plus #pertuzumab in patients with brain metastases @OncoAlert @myESMO https://t.co/xDTpiCuc3z
𝕏DESTINY-Breast09 (Exploratory CNS Analysis) #ESMO26 T-DXd + P demonstrated superior efficacy versus THP in HER2+ metastatic breast cancer with brain metastases (n=61). Systemic PFS: HR 0.30 CNS-PFS: HR 0.26 CNS-ORR: 51.6% vs 26.7% Systemic ORR: 83.9% vs 70.0% Supports T-DXd + P as first-line therapy, including patients with brain metastases.
𝕏DESTINY-Breast09 CNS Analysis Assessment of pts with BICR-assessed brain mets (treated and asymptomatic or clinically inactive) n=61 Deeper systemic and CNS response, and higher iORR @OncoAlert #ESMO26 https://t.co/lJhfvJgg2R
𝕏Doubling in intracranial ORR (51 vs 26%) and dramatic improvement in intracranial PFS with T-DXd/P vs THP in 1L HER2+ mBC. The DB09 regimen is the clear SoC for patients with brain metastases at metastatic diagnosis. #ESMO26 #ESMOAmbassadors https://t.co/i7NAbeJFk1
𝕏At #ESMO26 Rapid oral abstracts session on advanced #breastcancer @CristinaSaura3 presents an exploratory analysis of DB-09 on pts with brain mets 🧠 Systemic PFS and CNS-PFS was ⬆️ in pts treated with T-DXd + P vs THP SoC @OncoAlert https://t.co/DJvsxocLwM
𝕏Good morning from Madrid! Watching today’s DESTINY-Breast09 update: T-DXd + pertuzumab vs THP in HER2+ metastatic breast cancer with baseline brain metastases. What will this analysis add to the first-line discussion? @VHIO @myESMO @OncoDaily @OncoAlert #ESMO26 @stolaney1 @PTarantinoMD
𝕏Longer CNS-PFS w/ T-DXd + pertuzumab in the DESTINY-Breast09 (DB-09) brain mets subgroup (LBA49). 📌 Exploratory subgroup of randomized phase 3 DESTINY-Breast09: 61 pts w/ HER2+ advanced/metastatic breast cancer, baseline brain mets by BICR and ≥1 follow-up brain scan. T-DXd + pertuzumab (n=31) vs taxane + trastuzumab + pertuzumab (THP, n=30). 📌 Median follow-up 23.6 mo. mCNS-PFS NE vs 9.7 mo; HR 0.26 (95% CI 0.11-0.57). 📌 CNS-cORR 51.6% (95% CI 33.1-69.8) vs 26.7% (95% CI 12.3-45.9), by BICR. 📌 mPFS 36.5 vs 11.1 mo. 📌 Parent-trial drug-related ILD/pneumonitis: 12.1% (incl 2 grade 5) vs 1.0%. Brain mets subgroup AE rates aren't reported. Side note: prior CNS local therapy and the active/treated brain mets split aren't reported in the abstract. https://t.co/1kEnVk7VEw #ESMO26 #BCSM
Design — Phase 3, open-label; 1L T-DXd (Enhertu) + pertuzumab vs standard THP, HER2+ metastatic breast cancer (NCT04784715). (NEJM)
PFS (primary) — Median 40.7 vs 26.9 months; HR 0.56 (95% CI 0.44-0.71; p<0.0001) — 44% reduction, benefit regardless of HR status. (NEJM)
Overall survival — Immature (16% maturity); early numerical trend favors T-DXd + pertuzumab (HR 0.84; 95% CI 0.59-1.19). (interim)
Brain metastases (ESMO 2026, exploratory) — In 61 patients with brain metastases at baseline confirmed by BICR (31 vs 30), CNS-cORR was 51.6% vs 26.7%, median systemic PFS 36.5 vs 11.1 months (HR 0.30) and 12-month CNS-PFS 88.9% vs 42.5% with T-DXd + pertuzumab vs THP. Small subgroup, endpoints not prespecified; separate from the primary PFS result. (Saura, ESMO 2026 slides; DCO 26-Feb-2025)
Safety — Adjudicated drug-related ILD/pneumonitis 12.1% (2 fatal, 0.5%); neutropenia 78% all-grade (29% Grade 3/4); nausea 75%. (NEJM)
Regulatory — FDA approved December 15, 2025 for 1L HER2+ metastatic breast cancer; PATHWAY (4B5) companion Dx co-approved. (FDA.gov)
Sponsor / Drug — Daiichi Sankyo / AstraZeneca; T-DXd (Enhertu) ADC + pertuzumab (Perjeta). (FDA label)
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated October 26, 2026.
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| Endpoint | T-DXd + P (n=31) | THP (n=30) | HR (95% CI) |
|---|---|---|---|
| Median systemic PFS | 36.5 mo (19.1–NE) | 11.1 mo (7.5–15.4) | 0.30 (0.14–0.60) |
| 12-month systemic PFS | 86.5% | 39.4% | — |
| Median CNS-PFS | NE (19.1–NE) | 9.7 mo (4.2–19.2) | 0.26 (0.11–0.57) |
| 12-month CNS-PFS | 88.9% | 42.5% | — |
Top 10 by impressions - click to view on X
ADCs are rapidly moving to earlier line treatment for breast cancer. Will likely reach the (neo)adjuvant setting soon. Here’s a recap of key ADC phase 3 trials expected to shape practice in the...
< 2 wks to #ASCO25, here is a📝 of 🔑abstracts for general onc that could guide our SoC! - #ATOMIC - #MATTERHORN -...
Another money 💰 slide from #asco25 @ASCO . Treatment algorithm for HR +/ HER 2 -ve mBC @OncoAlert @medicalwatchBC
The curves everybody’s been waiting for. First line T-DXd + pertuzumab significantly prolonged PFS over THP for HER2+ MBC (40.7 vs 26.9 months, HR 0.56, p<0.001), doubled the rate of...
#OncTwitter #regulatory #bcsm 📣 #FDA has approved trastuzumab deruxtecan + pertuzumab for 1st-line tx of adults w/ HER2+...
When you have a packed @ASCO room at 7.30 am, you know that a change in practice is coming. #DESTINYBreast09 @stolaney1 #ASCO25 3 minutes to go
The #ASCO25 #OncoAlertTOP10 Abstracts in #BreastCancer These are some of our picks of TOP abstracts we look forward to be presented at the upcoming...
Destiny-Breast-09 will likely establish a new first-line therapy for HER2+ MBC. Here are my considerations going into #ASCO25 Patient population considerations: 1) De novo patients...
T-DXd + pertuzumab approved for 1st L HER-2+ #bcsm! Now for the debates around induction length, maintenance, re-induction etc. My opinion: I'll induce to...
Recent rationale in metastatic breast cancer for bringing ADCs into the 1st line has quoted very high 1st line attrition rates of patients not making it to second line. This study is likely more...
DESTINY-Breast09 is a clinical trial evaluating Trastuzumab deruxtecan (T-DXd) + pertuzumab in 1L HER2+ metastatic breast cancer. Sponsored by Daiichi Sankyo / AstraZeneca. KOL discussion spans multiple conferences with 106 tracked posts from 54 oncology opinion leaders generating 504.4K total impressions.
Phase 3, randomized (1:1:1), three-arm, multicenter trial comparing T-DXd (5.4 mg/kg) plus pertuzumab versus taxane plus trastuzumab plus pertuzumab (THP) in treatment-naive HER2-positive advanced/metastatic breast cancer.
Adults with HER2-positive (IHC 3+ or ISH+) unresectable or metastatic breast cancer with no prior chemotherapy or HER2-targeted therapy for advanced disease. A single prior line of endocrine therapy was permitted.
Fam-trastuzumab deruxtecan-nxki (Enhertu) 5.4 mg/kg IV every 3 weeks plus pertuzumab versus taxane (docetaxel or paclitaxel) plus trastuzumab plus pertuzumab (THP).
Primary: progression-free survival (PFS) by blinded independent central review (BICR). Key secondary: overall survival (OS), confirmed objective response rate (ORR).
T-DXd plus pertuzumab demonstrated a 44% reduction in risk of disease progression or death versus THP. Median PFS was 40.7 months (95% CI: 36.5-NE) versus 26.9 months (95% CI: 21.8-NE) (HR 0.56; 95% CI: 0.44-0.71; p<0.0001).
OS data remain immature (16% maturity). Early numerical trend favors T-DXd plus pertuzumab (HR 0.84; 95% CI: 0.59-1.19).
Adjudicated drug-related ILD/pneumonitis occurred in 12.1% of patients, including two fatal (Grade 5) events (0.5%). Neutropenia was common (78% all grades, 29% Grade 3/4). Nausea occurred in 75%. ILD was the leading cause of permanent discontinuation (6.6%).
DESTINY-Breast09 establishes T-DXd plus pertuzumab as a new first-line standard of care for HER2-positive metastatic breast cancer. FDA approved December 15, 2025. ILD risk and immature OS data remain areas of active debate.
Cristina Saura presented an exploratory analysis at ESMO 2026 (Madrid, October 26, 2026) of patients with brain metastases at baseline. Brain MRI/CT scans were reviewed retrospectively by blinded independent central review (BICR) after end of treatment. The analysis included 61 patients with BICR-confirmed brain metastases at baseline that were clinically inactive, or treated and asymptomatic, and who had at least one follow-up brain scan: 31 in the T-DXd + pertuzumab arm and 30 in the THP arm. The T-DXd + placebo arm was not included; per the slides, it remains blinded until the final PFS analysis. Data cutoff February 26, 2025; median follow-up 23.6 months. Regular on-treatment brain imaging was required only for patients whose brain metastases were identified by investigators at baseline; 29 of the 61 patients in this analysis (15 vs 14) were identified only on the retrospective central review.
| Endpoint (BICR) | T-DXd + pertuzumab (n=31) | THP (n=30) | HR (95% CI) |
|---|---|---|---|
| CNS confirmed ORR (CNS-cORR) | 51.6% (16/31; 95% CI 33.1–69.8) | 26.7% (8/30; 95% CI 12.3–45.9) | — |
| CNS complete response | 35.5% | 23.3% | — |
| Median CNS duration of response | NE (95% CI 14.3–NE) | 18.5 mo (95% CI 8.3–NE) | — |
| Systemic confirmed ORR | 83.9% (26/31; 95% CI 66.3–94.5) | 70.0% (21/30; 95% CI 50.6–85.3) | — |
| Median systemic duration of response | 35.1 mo (95% CI 17.1–NE) | 10.5 mo (95% CI 6.7–30.1) | — |
| Median systemic PFS (events) | 36.5 mo (95% CI 19.1–NE; 13 events) | 11.1 mo (95% CI 7.5–15.4; 22 events) | 0.30 (0.14–0.60) |
| 12-month systemic PFS | 86.5% | 39.4% | — |
| Median CNS-PFS (events) | NE (95% CI 19.1–NE; 9 events) | 9.7 mo (95% CI 4.2–19.2; 17 events) | 0.26 (0.11–0.57) |
| 12-month CNS-PFS | 88.9% | 42.5% | — |
The slides state that these endpoints were not prespecified in the protocol and that results should be interpreted with caution because of the small number of patients. No p-values were shown. De novo disease was more frequent in the T-DXd + pertuzumab arm of this subgroup (35.5% vs 23.3%). These results are separate from the trial's primary PFS result in all randomized patients (40.7 vs 26.9 months, HR 0.56; NEJM) and from overall survival, which remains immature. The FDA approval (December 15, 2025) covers first-line HER2-positive metastatic breast cancer; there is no separate brain-metastases indication.
DESTINY-Breast09 is a global, randomized, open-label Phase 3 trial (NCT04784715) in previously untreated (first-line) HER2-positive metastatic breast cancer comparing trastuzumab deruxtecan (T-DXd, Enhertu) plus pertuzumab versus the standard taxane + trastuzumab + pertuzumab (THP) regimen.
Yes. On December 15, 2025 the FDA approved Enhertu in combination with pertuzumab (Perjeta) for the first-line treatment of adults with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, based on DESTINY-Breast09. The PATHWAY (4B5) companion diagnostic was co-approved.
T-DXd plus pertuzumab reduced the risk of disease progression or death by 44% versus standard THP: median PFS 40.7 months versus 26.9 months (HR 0.56; 95% CI 0.44-0.71; p<0.0001), with benefit regardless of hormone-receptor status.
No. Overall survival data remain immature (about 16% maturity), with an early numerical trend favoring T-DXd plus pertuzumab (HR 0.84; 95% CI 0.59-1.19). Longer follow-up is needed.
Interstitial lung disease (ILD)/pneumonitis is the key monitored risk: adjudicated drug-related ILD occurred in 12.1% of patients, including two fatal (Grade 5) events (0.5%). ILD was the leading cause of permanent discontinuation; neutropenia and nausea were also common.
In an exploratory analysis presented by Cristina Saura at ESMO 2026, 61 patients had brain metastases at baseline confirmed by blinded independent central review (31 T-DXd + pertuzumab, 30 THP; data cutoff February 26, 2025). The CNS confirmed objective response rate was 51.6% vs 26.7%, median systemic PFS was 36.5 vs 11.1 months (HR 0.30), and 12-month CNS-PFS was 88.9% vs 42.5% (CNS-PFS HR 0.26). The subgroup is small and the endpoints were not prespecified, so the results are hypothesis-generating. They do not change the approved indication, which is first-line HER2-positive metastatic breast cancer.
