Six Major Trial Updates From ESMO Breast Cancer 2026
May 29, 2026
Key Points
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Positive findings in the VERITAC-2 trial led to the approval of vepdegestrant, a novel oral proteolysis-targeting chimera protein degrader, for ESR1–mutated advanced or metastatic breast cancer.
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Data from the PREcoopERA study suggest that combining ovarian suppression with oral selective estrogen receptor degraders (SERDs) is valuable in premenopausal patients.
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Updated results from the PHERgain trial showed that imaging and response–adapted treatment may allow patients with HER2–positive early breast cancer to forgo chemotherapy without compromising survival outcomes.
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Both the SATEEN and BRE-354 trials showed that antibody-drug conjugates (ADCs) with TOPO1 payloads have diminished activity in patients with previously treated HER2–positive metastatic breast cancer previously treated with another TOPO1 ADC.
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TROPION-Breast02 data updates continue to favor frontline datopotamab deruxtecan (Dato-DXd) over chemotherapy for patients with metastatic triple-negative breast cancer (TNBC).
ESMO Breast Cancer 2026 Data Highlights
Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, cohosts of the Oncology Brothers podcast, met with Erika Hamilton, MD, director of breast cancer research at Sarah Cannon Research Institute, to discuss meaningful breast cancer clinical trial data presented at the 2026 European Society for Medical Oncology Breast Cancer Annual Congress (ESMO Breast Cancer 2026). Dr. Hamilton reviewed data and takeaways from the VERITAC-2, PREcoopERA, PHERGain, SATEEN, BRE-354, and TROPION-Breast02 trials.
VERITAC-2 Leads to Approval of Vepdegestrant for ESR1–Mutated Disease
The phase 3 VERITAC-2 trial evaluated vepdegestrant versus fulvestrant in previously treated patients with estrogen receptor–positive, HER2–negative, ESR1–mutated advanced or metastatic breast cancer. The median progression-free survival (PFS) was 5 months (95% CI, 3.7-7.4) with vepdegestrant versus 2.1 months (95% CI, 1.9-3.5) with fulvestrant (hazard ratio [HR], 0.57; 95% CI, 0.42–0.77; P < .0001), and objective response rates (ORR) were 19% (95% CI, 12-27) and 4% (95% CI, 1.6-10), respectively. Based on the trial, the FDA approved vepdegestrant on May 1, 2026.
Vepdegestrant is a novel oral proteolysis-targeting chimera protein degrader, distinct from oral SERDs approved for this population. When selecting between these oral options for patients, vepdegestrant may offer lower nausea rates than elacestrant and lower diarrhea rates than imlunestrant.
PREcoopERA Shows Value of Ovarian Suppression in Premenopausal Patients
The phase 2 PREcoopERA trial compared giredestrant with or without ovarian function suppression (OFS) with an aromatase inhibitor (AI) plus OFS in premenopausal women with untreated ER–positive, HER2–negative early breast cancer. Mean changes in Ki-67 were -79.6% (95% CI, -82.4 to -76.4) with giredestrant plus OFS, -73.7% (95% CI, -79.3 to -66.6) with AI plus OFS, and -68.2% (95% CI, -73.3 to -62.2) with giredestrant alone. Giredestrant plus OFS was not superior to AI plus OFS, although giredestrant alone was not noninferior to giredestrant plus OFS.
While the trial showed giredestrant alone reduced Ki-67, the greater benefit seen in the giredestrant plus OFS arm suggest that OFS has a role alongside the nascent oral SERD class in premenopausal patients with early breast cancer, said Dr. Hamilton.
PHERGain: Treatment De-Escalation Strategy for Early Breast Cancer
At ESMO Breast Cancer 2026, authors presented 5-year invasive disease-free survival (iDFS) data from the phase 2 PHERgain trial. The PHERgain trial previously showed the feasibility of PET and pathological complete response (pCR)–guided omission of chemotherapy in patients with HER2–positive early breast cancer undergoing neoadjuvant therapy with trastuzumab plus pertuzumab (HP) with or without endocrine therapy. The 5-year iDFS rate in patients with a pCR who did not receive chemotherapy was 92.4% (95% CI, 86.7-98.5)
While the trial’s de-escalation strategy requires additional imaging, the data are very encouraging for allowing each patient’s disease biology to guide treatment planning, said Dr. Hamilton.
SATEEN and BRE-354 Find Lacking Activity With Sequential ADCs
The SATEEN trial sought to determine the efficacy of sacituzumab govitecan plus trastuzumab in patients with HER2–positive metastatic breast cancer previously treated with trastuzumab deruxtecan (T-DXd). The trial did not meet its ORR primary end point in stage 1 and was stopped early, according to the ESMO Breast Cancer 2026 presentation.
Another study, BRE-354, evaluated patritumab deruxtecan (HER3-DXd) in different metastatic breast cancer populations, including in patients with HER2–positive metastatic breast cancer previously treated with T-DXd or sacituzumab govitecan. While HER3-DXd was effective in ADC–naïve patients, it had considerably less activity in previously treated subgroups, according to the presentation by Dr. Hamilton.
Both trials support that ADCs with TOPO1 payloads are less effective in patients with HER2–positive metastatic breast cancer with prior ADC exposure. Despite this, sequencing ADCs may still be a reasonable treatment choice for patients who can not tolerate switching to chemotherapy, said Dr. Hamilton.
TROPION-Breast02 Continues To Support Frontline Dato-DXd in TNBC
The TROPION-Breast02 study previously found frontline datopotamab deruxtecan (Dato-DXd) improved PFS and overall survival compared with frontline chemotherapy in patients with metastatic TNBC ineligible for immunotherapy. Patient-reported outcome data presented at ESMO Breast Cancer 2026 showed Dato-DXd was favored for time to deterioration in secondary end points, including global health status and quality of life.
In the likely event that both Dato-DXd and sacituzumab govitecan are approved as frontline treatment options for metastatic TNBC, the doctors considered how to choose between the ADCs. Both agents provide a similar benefit, but they have different administration schedules and side effect profiles that may be more favorable based on individual patient characteristics and comorbidities, said Dr. Hamilton.