The 12 Most Anticipated Practice-Changing Abstracts at ESMO 2025: Community Oncologist’s Guide
The European Society of Medical Oncology (ESMO) Congress 2025 is here! The conference will be hosted in Berlin, Germany from October 17-21 and is packed with exciting research updates, some of which could redefine the current standard of care (SOC) in clinical practice. Below are 12 key abstracts anticipated to influence treatment algorithms and improve patient outcomes.
1. DESTINY-Breast11: Neoadjuvant T-DXd +/- THP vs. THP Alone in High-Risk Early-Stage HER2+
Study Overview: Phase 3 study evaluating neoadjuvant T-DXd +/- THP versus THP alone in previously untreated high-risk ( ≥ T3, node positive [N1-N3]) HER2-positive (HER2+) early breast cancer.
Primary Endpoint: Pathologic complete response (pCR; ypT0/Tis ypN0). Secondary endpoints include event-free survival (EFS) and safety.
Key Findings:
- pCR rate of 67.3% (T-DXd-THP) versus 56.3% (ddAC-THP) with improvement in both HR-positive (HR+,61.4% vs 52.3%) and HR-negative (HR-,83.1% vs 67.1%) breast cancer.
- EFS showed a favorable trend.
- Lower grade ≥ 3 adverse event (AE) rates with T-DXd-THP (37.5%) versus 55.8% ddAC, with lower incidence of ILD/pneumonitis (4.4% vs 5.1%) and left ventricular dysfunction (1.9% vs 9.0%) in the T-DXd-THP arm.
Takeaway: Neoadjuvant T-DXd-THP demonstrates favorable pCR improvement, favorable EFS trend, and improved safety profile compared to the SOC.
2. DESTINY-Breast05: Adjuvant T-DXd vs. T-DM1 in High-Risk HER2+ Breast Cancer with Residual Disease
Study Overview: Phase 3, multicenter, randomized, open-label, active-controlled study evaluating T-Dxd versus T-DM1 in patients with HER2+ primary breast cancer and residual invasive disease.
Primary Endpoints: Invasive disease-free survival (DFS). The secondary endpoint is DFS.
Key Findings: The study had a positive press release, indicating potentially practice-changing findings. The full findings will be presented at ESMO on October 18, 2025.
3. monarchE: 7-Year Analysis of Adjuvant Abemaciclib + Endocrine Therapy in High-Risk HR+/HER2- Early Breast Cancer
Study Overview: Phase 3 adjuvant trial evaluating CDK4/6i + endocrine therapy versus SOC for patients with HR+, HER2-, high-risk early breast cancer.
Primary Endpoints: Invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS).
Key Findings:
- 7-year iDFS: 77.4% versus 70.9%.
- 7-year DRFS: 80% versus 74.9%.
- Benefit was consistent across subgroups. Long-term safety data do not indicate delayed toxicities.
Takeaway: The addition of adjuvant abemaciclib to endocrine therapy resulted in meaningful improvement in OS and sustained iDFS and DRFS benefit.
4. NATALEE: 5-Year Analysis of Adjuvant Ribociclib + Endocrine Therapy in Broad-Population HR+/HER2- Early Breast Cancer
Study Overview: Phase 3, open-label, randomized study where patients with HR+, HER2- early breast cancer were randomized 1:1 to receive ribociclib + endocrine therapy versus nonsteroidal aromatase inhibitor (NSAI) alone.
Primary Endpoints: iDFS
Key Findings: Absolute iDFS:
- 3 year: 90.8% versus 88.0%.
- 4 year: 88.3% versus 83.9%.
- 5 year: 85.5% versus 81.0%.
IDFS benefit was observed across subgroups, including N0. Ribociclib (RIB) + NSAI demonstrated continued distant disease-free survival (DDFS) and DRFS benefit versus NSAI alone. OS hazard ratio (HR) was 0.80, which is a favorable trend, but not yet significant.
Takeaway: Five-year landmark analysis showed combination RIB+NSAI reduces the risk of invasive and distant disease recurrence compared to NSAI alone with a positive trend in OS.
5. VIKTORIA-1: Gedatolisib + Fulvestrant ± Palbociclib vs Fulvestrant After Progression on or After CDK4/6i+ET for HR+ Advanced Breast Cancer (PIK3CA WT)
Study Overview: Phase 3, open-label, randomized clinical trial analyzing efficacy and safety of gedatolisib + fulvestrant with or without palbociclib in patients with locally advanced or metastatic HR+/HER2- breast cancer after progression on or after CDK4/6 and aromatase inhibitor (AI) therapy.
Patients were randomized 1:1:1 to three treatment arms:
- Arm A: gedatolisib + fulvestrant + palbociclib.
- Arm B: gedatolisib + fulvestrant.
- Arm C: fulvestrant only.
Primary Endpoint: Progression-free survival (PFS).
Key Findings: Median PFS in arm A of 9.3 versus 2.0 months in arm C, and median PFS in arm B of 7.4 months versus 2.0 months in arm C. Additional data will be presented on October 18, 2025 at ESMO.
6. FORTITUDE-101: Bemarituzumab + mFOLFOX6 vs Placebo + mFOLFOX6 in FGFR2b-Overexpressing Advanced G/GEJ Cancer
Study Overview: Phase 3, bemarituzumab + mFOLFOX versus mFOLFOX for FGFR2b+ (10% expression or higher) first line therapy in advanced/metastatic gastric or gastric/gastroesophageal junction (GEJ) cancers.
Primary Endpoint: OS.
Key Findings: The trial met its primary OS endpoint. However, ocular AEs remain a concern as reports indicate findings are similar to the phase 2 data, occurring in both treatment arms but with a higher frequency and severity in the phase 3 bemarituzumab group.
7. AGITG DYNAMIC-III: ctDNA-Guided Adjuvant Chemotherapy De-Escalation and Escalation in Stage III Colon Cancer
Study Overview: Phase 2/3 ctDNA-stratified trial.
Primary Endpoints: Coprimary–RFi non-inferiority/superiority.
Key Findings: Results will be presented at ESMO on October 18, 2025.
8. STELLAR-303: Zanzalintinib + Atezolizumab vs Regorafenib in Refractory dMMR Metastatic Colorectal Cancer
Study Overview: Randomized, open-label, controlled phase 3 trial evaluating zanzalintinib + atezolizumab versus regorafenib in patients who have progressed or are intolerant to standard therapy.
Primary Endpoint: OS.
Key Findings: Early reports indicate the trial met its primary endpoint with positive improvements in OS. Results will be presented at ESMO on October 20, 2025.
9. KEYNOTE-905/EV-303: Perioperative Enfortumab Vedotin + Pembrolizumab vs Cystectomy Alone in Cisplatin-Ineligible MIBC
Study Overview: Phase 3 perioperative pembrolizumav + enfortumab vedotin (Pembro+EV) plus postoperative Pembro/EV, versus Pembro and postoperative Pembro, versus active surveillance after surgery in cisplatin-ineligible muscle-invasive bladder cancer (MIBC).
Presentation Date: Presidential Symposium I–October 18, 2025.
10. IMvigor011: ctDNA-Guided Adjuvant Atezolizumab vs Placebo in Resected Muscle-Invasive Bladder Cancer
Study Overview: Phase 3, randomized, placebo-controlled, double-blind study observing adjuvant treatment with atezolizumab versus placebo in patients with MIBC who are ctDNA+.
Primary Endpoint: DFS.
Presentation Date: Presidential Symposium III–October 20, 2025.
11. PSMAddition: Lutetium-177-PSMA-617 + ADT+ARPI vs ADT +ARPI First-Line Metastatic Hormone-Sensitive Prostate Cancer
Study Overview: International, open-label, prospective phase 3 study for patients with treatment-naïve or minimally treated PSMA+ mHSPC, randomized 1:1.
Primary Endpoint: Radiographic PFS.
Presentation Date: Presidential Symposium III–October 19, 2025
12. MDT-BRIDGE: Neoadjuvant Durva +Chemo -> Surgery and Adjuvant Durva vs ChemoXRT + Consolidation Durva in Resectable or Borderline Resectable Stage IIB-IIIB Non-small Cell Lung Cancer
Study Overview: Phase 2, single-arm, global study evaluating the safety and efficacy of neoadjuvant durvalumab and platinum-based chemotherapy, followed by either surgery and adjuvant durvalumab or definitive chemoradiation therapy and consolidation durvalumab in resectable and borderline resectable stage IIB-IIIB non-small cell lung cancer (NSCLC).
Primary Endpoint: Resection rate.
Presentation Date: October 18, 2025.
ESMO 2025: Shaping Tomorrow’s Oncology Practice
These 12 abstracts presented at ESMO 2025 showcase practice-changing research and reflect the accelerated pace of innovation in precision oncology. They highlight new data that will redefine standard treatment regimens across tumor types. Beyond the abstracts featured here are many other impactful studies.
Stay tuned on OncUpdates for rapid summaries, slide highlights, and commentary throughout ESMO 2025! Attending the conference? Feel free to tag @OncUpdates on X (Formerly Twitter) for all your conference highlights!