ESMO 2025: Notes From the Floor — What Will Really Change Oncology in 2026

By Vlad Bogin, MD, FACP, CEO, Cromos Pharma

The 2025 ESMO Congress, held in Berlin, brought together over 35,000 oncology professionals from around the world to showcase data that are already reshaping the clinical landscape. Below are the readouts I think will actually change clinical practice and influence the way sponsors design trials in 2026 and beyond.

1) ADCs Move into the Curative Setting

Antibody–drug conjugates (ADCs) continued to dominate the conversation at ESMO 2025, particularly in breast cancer.

• DESTINY-Breast11 (neoadjuvant): T-DXd (trastuzumab deruxtecan) followed by THP (trastuzumab and pertuzumab) achieved the highest ever pathological complete response rate in high-risk HER2+ early breast cancer (67.3% vs 56.1%; p = 0.003), marking a potential new standard of care.
• DESTINY-Breast05 confirmed the superiority of T-DXd over T-DM1 (trastuzumab emtansine) in the post-neoadjuvant setting (3-year IDFS 88.7% vs 77.8%; HR 0.47).
• In triple-negative breast cancer, (sacituzumab govitecan) and TROPION-Breast02 (datopotamab deruxtecan-dlnk) both demonstrated significant PFS improvements versus chemotherapy, positioning ADCs as the backbone of future frontline regimens.

Why it matters: ADCs are moving beyond salvage therapy to curative intent, prompting the need for earlier-line trial designs with built-in ILD monitoring and ctDNA-based response assessment.

2) Lung Cancer: Precision Meets Local Control

Two major signals emerged for NSCLC:

• The NorthStar phase II trial showed that adding local consolidative therapy (LCT) to osimertinib significantly prolonged PFS (25.3 vs 17.5 months; HR 0.66), emphasizing the role of multidisciplinary strategies in EGFR-mutant disease.
• Sevabertinib, an oral HER2-targeted TKI, produced response rates above 70% with no ILD events in HER2-mutant NSCLC patients. FDA priority review is ongoing following concurrent publication in NEJM.

Why it matters: With targeted TKIs now achieving CNS activity and tolerability, future NSCLC trials will need to integrate radiomics-guided LCT criteria and real-time ctDNA monitoring.

3) GU Cancers: Peri-Operative IO and a HER2 Breakthrough

• KEYNOTE-905/EV-303 showed that peri-operative enfortumab vedotin + pembrolizumab doubled both event-free and overall survival (EFS HR 0.40; OS HR 0.50) in cisplatin-ineligible MIBC, establishing a potential new standard.
• In urothelial cancer, the RC48-C016 Presidential Symposium presented disitamab vedotin + toripalimab results with a median OS of 31.5 vs 16.9 months (HR 0.54) — the first HER2-ADC plus IO regimen to outperform platinum chemotherapy.

Why it matters: HER2 testing in urothelial carcinoma (IHC 1+ to 3+) should become routine, as ADC/IO combinations expand the beneficiary population beyond HER2-high subsets.

4) HR+/HER2− Early Breast Cancer: Adjuvant CDK4/6 Inhibitors Deliver

Both major CDK4/6 inhibitor trials reached new milestones:

• monarchE: Abemaciclib plus endocrine therapy achieved a statistically significant overall survival benefit at 7 years.
• NATALEE: Ribociclib plus aromatase inhibitor showed a sustained 5-year IDFS advantage (HR 0.72) with meaningful benefit even in node-negative patients.

Why it matters: The data cement CDK4/6 inhibitors as a new standard for high-risk HR+/HER2− disease while reigniting discussions around treatment duration, cost, and patient quality of life.

5) Endometrial Cancer: A Five-Year Durability Signal

Pembrolizumab + lenvatinib (KEYNOTE-775 / Study 309) remains one of the longest-standing IO/TKI success stories: 5-year OS 16.7% vs 7.3%, median OS 18.0 vs 12.2 months, and no new safety signals. This durability confirms the regimen’s role in pMMR advanced endometrial carcinoma.

Why it matters:
Long-term survival data are rare in this population. These results reaffirm that IO + TKI combinations can achieve sustained benefit even in mismatch-repair-proficient disease, encouraging sponsors to design trials that track long-tail responders and late safety beyond traditional two-year endpoints.

6) Radioligand Therapy Moves Upstream

¹⁷⁷Lu-PSMA-617 in the PSMAddition trial demonstrated rPFS benefit in metastatic hormone-sensitive prostate cancer, supporting radioligand therapy in earlier lines.
Operational readiness with PSMA PET standardization, radiopharmacy capacity, and AE management, is now a strategic priority for sponsors.

Why it matters:
Radioligand therapy is transitioning from niche to mainstream. As evidence accumulates in hormone-sensitive settings, sponsors will need to integrate imaging, dosimetry, and nuclear medicine expertise early in trial design to compete in this rapidly expanding field.

Advancing the Future of Oncology Research

ESMO 2025 demonstrated that oncology is entering a new era, defined by precision, integration, and collaboration. From five-year durability signals and breakthrough radioligand therapies to transformative biomarker-driven strategies, the field continues to evolve toward smarter, more personalized cancer care.

At Cromos Pharma, we are proud to be part of this momentum. Our mission is to accelerate access to innovative therapies through operational excellence, data-driven decision-making, and a steadfast commitment to patients and partners worldwide.

As oncology research becomes increasingly complex, our agility, scientific insight, and global experience empower sponsors to navigate every stage of development—from feasibility and regulatory strategy to patient recruitment and trial execution.