4 Significant Trials for HER2+ Breast Cancer at SABCS 2025
February 10, 2026
Key Points
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The DESTINY-Breast05 trial provided strong evidence for using trastuzumab deruxtecan (T-DXd) as adjuvant treatment for high-risk, HER2–positive early breast cancer with residual disease after neoadjuvant therapy.
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In DESTINY-Breast11, T-DXd as a neoadjuvant regimen for HER2–positive early breast cancer showed some improvements in response rate and safety. However, the evidence is less compelling than the data on adjuvant treatment.
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HER2CLIMB-05 and PATINA supported the addition of tucatinib and palbociclib, respectively, to standard maintenance regimens after induction therapy in HER2–positive metastatic breast cancer.
SABCS 2025 Presentations in HER2+ Breast Cancer
Harold Burstein, MD, PhD, of Dana-Farber Cancer Institute, joined the Oncology Brothers podcast with cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, to discuss presentations in HER2–positive breast cancer from the 2025 San Antonio Breast Cancer Symposium (SABCS 2025). The doctors discussed the latest updates from the DESTINY-Breast11, DESTINY-Breast05, HER2-CLIMB05, and PATINA trials.
T-DXd as Neoadjuvant Regimen in DESTINY-Breast11
The DESTINY-Breast11 trial evaluated either T-DXd alone or T-DXd followed by paclitaxel, trastuzumab, and pertuzumab (T-DXd-THP) against dose-dense doxorubicin plus cyclophosphamide followed by THP (ddAC-THP) as neoadjuvant treatment for patients with high-risk, HER2–positive early breast cancer. In previous reports, DESTINY-Breast11 showed that T-DXd-THP significantly improved pathologic complete response and safety versus ddAC-THP.
The rates of all-grade, drug-related interstitial lung disease (ILD) or pneumonitis were 4.9% with T-DXd, 4.4% with T-DXd-THP, and 5.1% with ddAC-THP. Compared with ddAC-THP, T-DXd-THP had lower rates of all-grade left ventricular dysfunction (1.3% vs 6.1%) and neutropenia (29.1% vs 44.2%), but higher rates of nausea (64.7% vs 51.6%), vomiting (28.8% vs 21.2%), and peripheral neuropathy (45% vs 35.9%). However, events were “generally low grade and nonserious,” according to the SABCS 2025 presentation.
The doctors noted that ddAC-THP, as a comparator, does not reflect clinical practice in the US, where the primary neoadjuvant regimen is 6 cycles of TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab). Overall, it’s debatable whether T-DXd should be prioritized over other conventional neoadjuvant regimens for HER2–positive early breast cancer based on these results, particularly in light of data for adjuvant T-DXd from the DESTINY-Breast05 trial, said Dr. Burstein.
Adjuvant T-DXd Versus T-DM1 in DESTINY-Breast05
The DESTINY-Breast05 trial compared adjuvant T-DXd with trastuzumab emtansine (T-DM1) in high-risk, HER2–positive primary breast cancer with residual invasive disease after neoadjuvant therapy. In the trial, T-DXd improved invasive disease-free survival versus T-DM1 across subgroups, including HER2 IHC 3+ (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70), HER2 ISH–positive (HR, 0.35; 95% CI, 0.13-0.97), prior anthracycline therapy (HR, 0.45; 95% CI, 0.29-0.69), and prior platinum-based therapy (HR, 0.54; 95% CI, 0.31-0.93).
In contrast to DESTINY-Breast11, the DESTINY-Breast05 data are more convincing for changing clinical practice, as T-DM1 has been the standard of care in this population for close to a decade, and T-DXd “clearly outperformed” it, said Dr. Burstein. For community oncologists, implementing T-DXd for HER2–positive breast cancer with residual disease after neoadjuvant treatment will require additional monitoring for ILD, although the doctors agreed the benefit shown in the trial likely outweighs the risk.
Tucatinib Maintenance in Metastatic Breast Cancer in HER2CLIMB-05
In the HER2CLIMB-05 trial, researchers investigated adding tucatinib to maintenance trastuzumab plus pertuzumab (HP) after first-line induction therapy with THP in patients with HER2–positive metastatic breast cancer. The addition of tucatinib to HP significantly improved progression-free survival (PFS; HR, 0.641; 95% CI, 0.514-0.799; P < .0001) for patients regardless of hormone receptor (HR) status, though a stronger PFS benefit was seen in the HR–negative subgroup (HR, 0.554, 0.403-0.761; P = .0002).
Dr. Burstein advised caution when interpreting the survival data, as the difference may be driven by international patients who lack access to novel therapies approved in the US for subsequent lines of therapy. “Did these patients get, for instance, T-DXd at progression, which would certainly be standard in the US,” said Dr. Burstein.
The doctors briefly discussed how maintenance strategies will adjust to the recent approval of first-line T-DXd plus pertuzumab for metastatic breast cancer based on DESTINY-Breast09. Patients will likely receive induction therapy and then transition to a maintenance regimen. The choice of maintenance regimen may be shaped by each patient’s response to induction therapy, HR status, and tolerability, Dr. Burstein said. Given the length of median PFS reported for even the control arm in HER2CLIMB-05, oncologists may also be able to introduce additional agents in later lines after progression, he added.
Palbociclib Plus Standard First-Line Maintenance in PATINA
The PATINA trial found the addition of palbociclib to standard first-line maintenance with anti-HER2 plus endocrine therapy improved PFS for patients with HR–positive, HER2–positive metastatic breast cancer. A secondary analysis presented at SABCS 2025 reported that the palbociclib group also had slightly lower rates of central nervous system (CNS) progression (13.4% vs 19.5%). The CNS benefit of palbociclib is promising, and the PATINA trial further establishes that endocrine therapy plus anti-HER2 treatment is effective in HR–positive, HER2–positive breast cancer overall, said Dr. Burstein.
Dr. Rahul Gosain asked Dr. Burstein how he would incorporate the DESTINY-Breast09, HER2CLIMB-05, and PATINA data into the treatment of HER2–positive metastatic breast cancer. Based on all three trials, most patients will receive T-DXd plus pertuzumab or THP as induction therapy. Assuming patients respond well, they’ll eventually transition to a maintenance regimen that includes endocrine therapy and, for HR–positive patients, palbociclib or, for HR–negative patients, tucatinib.
Ultimately, these trials operationalize what has been clinical practice for several years across different breast cancer populations, Dr. Burstein said.