In Madrid, at the 2026 ESMO Congress, a small and exploratory look at a single corner of a large breast cancer trial has drawn attention to patients whose disease had already reached the brain. Among 61 women with HER2-positive breast cancer and brain metastases, a combination of trastuzumab deruxtecan and pertuzumab kept the disease at bay far longer than the long-standing THP regimen, both in the body and in the brain. The finding is encouraging rather than conclusive, since the group is small and the analysis was not planned as a confirmation, yet it adds to a growing picture in which this
T-DXd Plus Pertuzumab Extends Systemic and Intracranial Control in HER2+ Breast Cancer With Brain Metastases
CNS PFS was not yet reached with T-DXd versus 9.7 months with THP
Mark
Why does a 61-patient subgroup get attention at ESMO?
Mimi
Brain metastases are where many HER2-positive patients run into trouble, and this is first-line data on whether T-DXd works there, not just elsewhere in the body.
Mark
What's the headline number?
Mimi
Systemic PFS of 36.5 months versus 11.1 with THP, and CNS PFS not yet reached in the T-DXd arm versus 9.7 months.
Luke
Keep the size in view, though. It's 31 versus 30 patients, and the analysis was exploratory. The confidence interval on systemic PFS runs from 19.1 to not estimable.
Mark
Does that undercut the result?
Luke
It limits how firmly anyone can lean on it. The direction is consistent, but the precision is low.
Mimi
And the arms weren't perfectly matched. The T-DXd group had more patients from Asia, more IHC 3+ tumors and more de novo disease.
Luke
Whether those differences moved the outcome isn't something this reporting tells us.
Mark
How were the brain scans handled?
Mimi
Routine on-treatment imaging was only required when investigators had spotted baseline metastases, so reviewers re-read all scans after treatment ended.
Luke
Which makes it a retrospective review. That's useful, but it isn't the same as a trial designed around CNS endpoints.
Mark
So what's solid?
Luke
The FDA approval rests on the full trial, with hazard ratio 0.56. This subgroup is supportive, not confirmatory.
Der Puls
- Brain metastases in HER2-positive breast cancer have long been among the hardest complications to control, and this analysis focused on exactly those patients.
- In 61 women, systemic progression-free survival stretched to 36.5 months on the new combination against 11.1 months on THP, a gap that landed with weight among clinicians.
- Brain-specific control separated just as sharply, with CNS progression-free survival not reached on the new regimen versus 9.7 months on THP.
- The evidence is still small and exploratory, so researchers are navigating cautiously toward larger confirmatory data that will decide whether this becomes a standard first-line answer.
In Madrid, at the 2026 ESMO Congress, a small and exploratory look at a single corner of a large breast cancer trial has drawn attention to patients whose disease had already reached the brain. Among 61 women with HER2-positive breast cancer and brain metastases, a combination of trastuzumab deruxtecan and pertuzumab kept the disease at bay far longer than the long-standing THP regimen, both in the body and in the brain. The finding is encouraging rather than conclusive, since the group is small and the analysis was not planned as a confirmation, yet it adds to a growing picture in which this newer approach reaches places that older treatments struggled to hold. Its meaning will be settled by larger studies still to come.
At the 2026 ESMO Congress in Madrid, Cristina Saura of Vall d'Hebron University Hospital and the Vall d'Hebron Institute of Oncology in Barcelona turned attention to a narrow group within a large trial: the 61 patients who already had brain metastases when they enrolled. Among them, trastuzumab deruxtecan (Enhertu) combined with pertuzumab held cancer back far longer than THP, the standard combination of a taxane, trastuzumab and pertuzumab.
The parent study, DESTINY-Breast09, is a randomized phase 3 trial in HER2-positive advanced breast cancer. Patients with inactive or asymptomatic brain metastases were allowed to join, and the reviewers re-examined every brain scan after treatment to judge how the disease had behaved in the brain. The 31 patients on the new combination and 30 on THP were broadly similar, though the newer arm had more patients from Asia and more with de novo disease.
The contrast was striking. Median systemic progression-free survival was 36.5 months against 11.1 months, and brain-specific progression-free survival was not reached against 9.7 months. Brain responses were also more frequent, at 51.6% versus 26.7%. In a matched subgroup, the gap widened further.
Saura called these results a strengthening of the case for CNS activity in first-line HER2-positive disease. The caveat is that the group is small and the analysis exploratory, so the findings point the way rather than settle the question. They build on the December 2025 FDA approval of the combination, where the full trial showed longer progression-free survival, and larger confirmatory data are still awaited.
At the 2026 ESMO Congress in Madrid, Cristina Saura of Vall d'Hebron University Hospital and the Vall d'Hebron Institute of Oncology in Barcelona presented an exploratory look at a narrow slice of a large breast cancer trial: the 61 patients who had brain metastases when they enrolled. In that group, trastuzumab deruxtecan (T-DXd, sold as Enhertu) plus pertuzumab held cancer back far longer than the standard combination of a taxane, trastuzumab and pertuzumab, known as THP.
The parent study is DESTINY-Breast09, a randomized, multicenter phase 3 trial in HER2-positive advanced or metastatic breast cancer. Patients had not yet received systemic therapy for advanced disease, apart from at most one line of endocrine therapy. Those who had earlier neoadjuvant or adjuvant chemotherapy or HER2-targeted treatment could join if their last dose was more than six months before. Patients with inactive or asymptomatic brain metastases were allowed. They were randomized 1:1:1 to T-DXd at 5.4 mg/kg plus pertuzumab (383 patients), THP (387), or T-DXd plus placebo (387). The taxane was paclitaxel or docetaxel. The primary endpoint was progression-free survival (PFS) by blinded independent central review, with overall survival the key secondary endpoint.
Every participant had a brain MRI or CT at baseline and at the end of treatment. Routine scans during treatment were required only when the investigator had identified brain metastases at baseline. For this analysis, the central reviewers went back through all brain scans after treatment ended and assessed systemic and central nervous system (CNS) responses in the T-DXd/pertuzumab and THP arms, which together held 770 patients. To qualify, patients needed brain metastases confirmed by central review that were either clinically inactive or treated and asymptomatic without corticosteroids or anticonvulsants. They also needed at least two weeks between whole brain radiotherapy and enrollment, and at least one follow-up brain scan. The data cutoff was February 26, 2025, with median follow-up of 23.6 months.
The 61 patients split into 31 on T-DXd plus pertuzumab and 30 on THP. Median ages were 56 and 54, and 64.5% and 60.0% had an ECOG performance status of 0. The T-DXd arm had more patients from Asia (54.8% vs 36.7%), more with HER2 IHC 3+ tumors (90.3% vs 80.0%) and more with de novo disease (35.5% vs 23.3%). Prior brain radiotherapy had been given to 22.6% and 20.0%, respectively.
Median systemic PFS was 36.5 months with T-DXd plus pertuzumab against 11.1 months with THP (hazard ratio 0.30), and 12-month systemic PFS rates were 86.5% vs 39.4%. For CNS PFS, the median was not estimable in the T-DXd arm, against 9.7 months with THP (hazard ratio 0.26); at 12 months, 88.9% vs 42.5% were free of CNS progression.
Confirmed objective response rates were 83.9% vs 70.0%. Confirmed CNS response rates were 51.6% vs 26.7%, and CNS complete responses occurred in 35.5% vs 23.3% of patients. Systemic responses in the T-DXd arm were complete in 9.7% and partial in 74.2%, while all THP responses were partial. Median systemic duration of response was 35.1 months vs 10.5 months. Median CNS duration of response was not estimable with T-DXd plus pertuzumab and 18.5 months with THP. Objective CNS responses were seen in 16 patients on T-DXd plus pertuzumab and 8 on THP.
In a subgroup of 32 patients whose brain metastases were identified by both central review and the investigator, 16 per arm, systemic response rates were 87.5% vs 62.5% and CNS response rates were 75.0% vs 31.3%. "These findings further strengthen the body of evidence which supports the CNS activity of [T-DXd] in the first line [HER2-positive] setting," Saura said.
The context is the full trial, which led the FDA on December 15, 2025 to approve T-DXd plus pertuzumab as first-line therapy for unresectable or metastatic HER2-positive breast cancer. There, median PFS was 40.7 months vs 26.9 months (hazard ratio 0.56), and response rates were 87% vs 81%. Overall survival data were immature at the time. The investigators concluded that the brain metastasis findings support first-line use of the combination.
Bemerkenswerte Zitate
These findings further strengthen the body of evidence which supports the CNS activity of T-DXd in the first-line HER2-positive setting.— Cristina Saura, MD, PhD, Vall d'Hebron University Hospital
Möchten Sie die ganze Geschichte?
Das Original lesen bei OncLive ↗
Politics & Governance