ESMO 2025 Breast Cancer Data May Redefine Treatment Standards Across Patient Subgroups

The 2025 ESMO Congress provided an opportunity for several exciting breast cancer studies to take center stage. From the HER2-positive to hormone receptor–positive to triple-negative disease subtypes, notable clinical updates were well represented.

At the conference, OncLive® asked breast cancer experts to share their perspectives on the most practice-informing data presented at the meeting. We heard from:

• Rebecca Dent, MD, MSc, senior consultant at the National Cancer Center in Singapore
• Erica L. Mayer, MD, MPH, the director of Breast Cancer Clinical Research at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston, Massachusetts
• Paolo Tarantino, MD, PhD, a research fellow in medicine at Dana-Farber Cancer Institute and Harvard Medical School
• Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and associate director at the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School

Read more about these study findings and why experts are excited for the changes they may bring to treatment paradigms across breast cancer subtypes.

DESTINY-Breast11: Top Data1

• In this phase 3 trial (NCT05113251), neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus THP (a taxane plus trastuzumab [Herceptin] and pertuzumab [Perjeta]; n = 321) yielded a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) compared with dose-dense doxorubicin and cyclophosplamde plus THP (ddAC-THP; n = 320) in patients with high-risk HER2-positive early breast cancer, achieving a pCR rate of 67.3% vs 56.3% (Δ, 11.2%; 95% CI, 4.0-18.3; P = .003).
• The T-DXd/THP regimen’s overall safety profile was favorable compared with ddAC-THP, with lower rates of grade 3 or higher adverse effects (AEs; 37.5% vs 55.8%) and AEs (10.6% vs 20.2%), including reduced left ventricular dysfunction.
• The improvement in pCR with T-DXd/THP vs ddAC-THP was observed regardless of hormone receptor status, achieving high pCR rates in both hormone receptor–negative (83.1%, n = 83; 67.1%, n = 85; Δ, 16.1%; 95% CI, 3.0%-28.8%) and hormone receptor–positive (61.4%, n = 236; 52.3%, n = 235; Δ, 9.1%; 95% CI, 0.2%-17.9%) populations.

Read more about DESTINY-Breast11 through OncLive’s coverage here!

DESTINY-Breast05: Notable Findings2

• In this phase 3 trial (NCT04622319), T-DXd (n = 818) demonstrated superior efficacy over ado-trastuzumab emtansine (T-DM1; Kadcyla; n = 817) for the trial’s primary end point of invasive disease–free survival (IDFS) in patients with high-risk HER2-positive primary breast cancer with residual invasive disease after neoadjuvant therapy, achieving a 53% reduction in the risk of invasive disease recurrence or death (HR, 0.47; 95% CI, 0.34-0.66; P < .0001), The 3-year IDFS rates were 92.4% (95% CI, 89.7%-94.4%) with T-DXd vs 83.7% (95% CI, 80.2%-86.7%) with T-DM1.
• T-DXd was associated with lower rates of recurrence in key areas compared with T-DM1, specifically resulting in numerically fewer central nervous system metastases and deaths.
• The overall safety profile of T-DXd was manageable, although adjudicated drug-related interstitial lung disease (ILD)/pneumonitis was reported in 9.6% of patients who received T-DXd compared with 1.6% of those who received T-DM1. Most T-DXd-related ILD cases were grade 1 or 2 and reversible.

Read on for OncLive’s exclusive coverage of DESTINY-Breast05!

TROPION-Breast02: Primary Result Highlights3

• In this phase 3 trial (NCT05374512), datopotamab deruxtecan-dlnk (Dato-DXd; Datroway; n = 323) significantly improved progression-free survival (PFS) by blinded independent central review vs investigator’s choice of chemotherapy (n = 321) in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC), achieving a median PFS of 10.8 months (95% CI, 8.6-13.0) compared with 5.6 months (95% CI, 5.0-7.0; HR, 0.57; 95% CI, 0.47-0.69; P < .0001).
• Dato-DXd generated a statistically significant and clinically meaningful improvement in overall survival (OS), reducing the risk of death by 21% (HR, 0.79; 95% CI, 0.64-0.98; P = .0291). The median OS was 23.7 months (95% CI, 19.8-25.6) with Dato-DXd compared with 18.7 months (95% CI, 16.0-21.8) with chemotherapy.
• The efficacy of Dato-DXd was highlighted by a confirmed overall response rate (ORR) of 62.5%, which was more than double the ORR observed in the chemotherapy arm (29.3%; OR, 4.24; 95% CI, 3.03-5.95).

Check out OncLive’s coverage of the TROPION-Breast02 findings here!

ASCENT-03: Primary Data Spotlight4

• In this phase 3 trial (NCT05382299), sacituzumab govitecan-hziy (Trodelvy; n = 279) generated a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy (n = 279) in patients with previously untreated metastatic TNBC, yielding a median PFS of 9.7 months (95% CI, 8.1-11.1) vs 6.9 months (95% CI, 5.6-8.2), respectively (HR, 0.62; 95% CI, 0.50-0.77; P < .0001).
• Although objective response rates were similar between the 2 treatment groups (sacituzumab govitecan, 48%, 95% CI, 42%-54%; chemotherapy, 46%, 95% CI, 40%-52%), the median duration of response was substantially longer with sacituzumab govitecan, at 12.2 months (95% CI, 9.7-13.8) compared with 7.2 months (95% CI, 5.7-8.4) with chemotherapy.
• Sacituzumab govitecan was associated with a lower rate of treatment discontinuation due to treatment-emergent AEs (TEAEs) compared with chemotherapy (4% vs 12%, respectively), even though the rates of grade TEAEs were similar (66% vs 62%).

Learn more from ASCENT-03 through OncLive’s exclusive coverage.

SERENA-6 Patient-Reported Outcome Analysis: Key Takeaways5

• Previously reported findings from the phase 3 SERENA-6 trial (NCT04964934) demonstrated a statistically significant and clinically meaningful improvement in PFS with camizestrant plus a CDK4/6 inhibitor (n = 157) in patients with hormone receptor–positive, HER2-negative advanced breast cancer with emergent ESR1 mutations, with a median PFS of 16.0 months (95% CI, 12.7-18.2) compared with 9.2 months (95% CI, 7.2-9.5) with an aromatase inhibitor (AI)plus a CDK4/6 inhibitor (n = 158; adjusted HR, 0.44; 95% CI, 0.31-0.60; P<.0001).
• At ESMO 2025, data from the patient-reported outcome analysis showed that camizestrant plus a CDK4/6 inhibitor significantly delayed the time to clinically meaningful deterioration (TTD) in Global Health Status/Quality of Life, with a median TTD of 21.0 months compared with 6.4 months with an AI plus a CDK4/6 inhibitor(adjusted HR, 0.54; 95% CI, 0.34-0.84).
• The use of camizestrant plus a CDK4/6 inhibitor consistently delayed the TTD and reduced the risk of deterioration in specific patient-reported cancer symptoms, such as pain, where the median TTD was 16.6 months compared with 6.5 months with an AI plus a CDK4/6 inhibitor (adjusted HR, 0.57; 95% CI, 0.37-0.86).

Check out more from SERENA-6 in this OncLive article!

evERA trial: Primary Analysis Takeaway Points6

• In this phase 3 trial (NCT05306340), in patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer with ESR1 mutations who had previously received CDK4/6 inhibition, the combination of giredestrant plus everolimus (Afinitor; n = 102) produced a statistically significant and clinically meaningful 62% reduction in the risk of progression or death compared withstandard-of-care endocrine therapy plus everolimus (n = 105; HR, 0.38; 95% CI, 0.27-0.54; P < .0001).
• In the intent-to-treat population, treatment with the giredestrant and everolimus combination (n = 183) led to a clinically meaningful 44% reduction in the risk of progression or death compared with endocrine therapy plus everolimus (n = 190; HR, 0.56; 95% CI, 0.44-0.71; P < .0001).
• The safety profile of giredestrant plus everolimus was manageable and consistent with the known safety profiles of the individual drugs, supporting the conclusion that this combination may represent a new effective all-oral treatment option in the post-CDK4/6 inhibitor setting for ER-positive, HER2-negative advanced breast cancer.

Take a closer look at the evERA data in this OncLive article!

VIKTORIA-1: Initial Findings7

• Gedatolisib plus palbociclib (Ibrance) and fulvestrant (Faslodex; n = 131) yielded a statistically significant and clinically meaningful improvement in PFS vs fulvestrant monotherapy (n = 131) for patients with PIK3CA wild-type, hormone receptor–positive, HER2-negative advanced breast cancer. The median PFS was 9.3 months (95% CI, 7.2-16.6) with the triplet compared with 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (adjusted HR, 0.24; 95% CI, 0.17-0.35; P < .0001).
• Gedatolisib plus fulvestrant (n = 130) was also statistically superior to fulvestrant alone regarding PFS. The median PFS was 7.4 months (95% CI, 5.5-9.9) with the doublet compared with 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (adjusted HR, 0.33; 95% CI, 0.24-0.48; P < .0001).
• The overall safety and tolerability profiles of the gedatolisib-based regimens were favorable, with low rates of PI3K/AKT/mTOR pathway–related AEs, such as hyperglycemia (triplet, 9.2%; doublet, 11.5%) and diarrhea (16.9%; 12.3%), and low rates of discontinuation due to treatment-related AEs (2.3%; 3.1%).

Read more about VIKTORIA-1 through OncLive’s coverage of the trial!

References

1. Harbeck N, Modi S, Pusztai L, et al. DESTINY-Breast11: neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 291O.
2. Geyer CE, Park YH, Shao Z, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): interim analysis of DESTINY-Breast05. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA1.
3. Dent RA, Shao Z, Schmid P, et al. First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase 3 TROPION-Breast02 trial. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA21.
4. Cortés JC, Bardia A, Punie K, et al. Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i). Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin Germany. Abstract LBA20.
5. Mayer EL, Bidard F-C, Park YH, et al. Patient-reported outcomes from the SERENA-6 trial of camizestrant + CDK4/6 inhibitor for emergent ESR1m during first-line endocrine-based therapy and ahead of disease progression in patients with HR+/HER2– advanced breast cancer. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 486MO.
6. Mayer E, Tolaney SM, Martin M, et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA16.
7. Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib Plus Fulvestrant, With & Without Palbociclib, vs Fulvestrant in Patients With HR+/HER2-/PIK3CA Wild-Type Advanced Breast Cancer: First Results from VIKTORIA-1. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA17.