5 clinical advances and related implications from ESMO 2025

With more than 35,000 attendees from the oncology community and nearly 3,000 abstracts presented, there was no shortage of discussions regarding the ongoing wave of transformative advances in cancer research and treatment at the European Society for Medical Oncology (ESMO) 2025 Congress.

From emphasising a shift toward curative intent and earlier-stage personalised care to regional research and development dynamics and related clinical trial design implications, emerging science is reshaping clinical care, and the rapid evolution of patient-centric research is ramping up.

Below are five particularly insightful takeaways from this year’s ESMO Congress that merit deeper reflection on where cancer care can go.

1.The maturing role of antibody-drug conjugates: How early and where?

It is difficult to leave ESMO 2025 without discussing the turning point in the evolution of ADCs, with over 130 abstracts presented, underscoring the modality’s maturity and how it’s reshaping oncology pipelines.

The shift of more ADCs to earlier points of treatment regimens may reflect a broader transformation in patient expectations. As EMSO President Fabrice André, MD, PhD, emphasised in his opening speech, optimising care for individual patients is the key to improving outcomes for all. This raises the stakes for further evaluating curative intent, toxicity management, and long-term quality of life in emerging modalities.

The next wave of ADC innovation is focused on earlier-stage cancers, with curative intent driving development strategies. Several studies unveiled at ESMO underscored the promise of ADCs across tumour types and at different stages of treatment:

• Significant data presented at ESMO has positioned trastuzumab deruxtecan (T-DXd) as a game-changing therapy in HER2-positive breast cancer, with implications reaching beyond metastatic disease into curative settings. Collectively, findings from DESTINY-Breast05 and DESTINY-Breast11 Phase III studies presented in a presidential symposium demonstrated superior efficacy of treatment with T-DXd over previous standards in both adjuvant (post-surgery) and neoadjuvant (pre-surgery) contexts, respectively, including improved invasive disease-free survival and higher pathologic complete response rates with fewer serious side effects.
  • In the DESTINY-Breast05, T-DXd improved invasive disease-free survival and disease-free survival by 53% compared with trastuzumab emtansine.
  • The DESTINY-Breast11 trial showed in patients with high-risk HER2-positive early breast cancer that the ADC followed by standard HER2-targeted therapy (paclitaxel, trastuzumab, and pertuzumab) led to a significant increase in the rate of pathological complete response at surgery (67.3% versus 56.3%; p=0.003).
• ADCs also showed improvement compared to standard of care in earlier lines of the metastatic setting. For example, datopotamab deruxtecan improved progression-free survival by 38% in first line setting of metastatic triple-negative breast cancer.
• In non-small cell lung cancer, sacituzumab tirumotecan showed a 51% reduction in the risk of disease progression and a 40% improvement in overall survival in the interim analysis in EGFR-mutated NSCLC previously treated with tyrosine kinase inhibitor.
• In muscle-invasive bladder cancer, perioperative enfortumab vedotin combined with immunotherapy pembrolizumab reduced the risk of death by 53% in cisplatin-ineligible patients, with a 50% improvement in overall survival versus standard surgery alone. These findings emphasise the need for more evaluation to gauge the potential to be a new standard of care for this patient population.

There were many conversations regarding the future of ADCs. To enhance efficacy and treatment flexibility, innovations like dual payload designs, which allow more strategic sequencing across cancer types, are worth watching. They help to avoid treatment resistance and ensure long-term feasibility of ADCs as alternatives to chemotherapy.

2.What were once undruggable targets

Researchers presenting at ESMO 2025 highlighted tremendous progress in targeting previously undruggable cancer mutations, particularly the KRAS gene.

Once considered resistant to therapeutic intervention due to its structural challenges, KRAS, especially the G12C and G12D variants, is now being successfully targeted by novel inhibitors with careful monitoring of potential toxicity challenges. There were several relevant data results presented concerning the G12D mutation present in approximately 39% of people diagnosed with pancreatic cancer. This included results from a Phase I/II study in which GFH375, a selective KRAS G12D inhibitor, showed a 41% objective response rate and 97% disease control in heavily pretreated pancreatic cancer patients. Similarly, HRS-7058, a KRAS G12C inhibitor, demonstrated promising activity in NSCLC and colorectal cancer, including in patients previously treated with other KRAS inhibitors.

Beyond KRAS, presentations spotlighted innovative modalities, such as bispecific antibodies, which can redefine therapeutic strategies across solid tumours, including advanced squamous NSCLC, microsatellite stable colorectal cancer , and HER2-positive gastric or gastroesophageal junction cancers.

These findings and others underscore a paradigm shift in precision oncology that reflects a growing ability to use molecular profiling and targeted therapies to open doors in oncology drug development for historically resistant cancers.

3.ctDNA-guided treatment: Precision in real time

Circulating tumour DNA (ctDNA) assays have emerged as dynamic biomarkers for therapeutic monitoring, as well as detection of minimal residual disease. This enables adjustments to therapy in real-time, as well as more precise treatment decisions. Advances in digital droplet Polymerase Chain Reaction (ddPCR) and Next-Generation Sequencing (NGS) are pushing boundaries for ctDNA detection sensitivity.

As shared at ESMO, though these assays are showing to be beneficial in reducing overtreatment, there is a broader promise to help catch disease recurrence early and better guide therapeutic drug monitoring. Standout examples include:

• In bladder cancer, the IMvigor011 Phase III study demonstrated that ctDNA-positive patients receiving adjuvant atezolizumab had significantly improved disease-free and overall survival, while ctDNA-negative patients could potentially avoid unnecessary treatment.
• In patients with BRAF V600E-mutant metastatic colorectal cancer, findings from the pivotal showed that a regimen of the small molecule kinase inhibitor encorafenib, monoclonal antibody cetuximab, and combination chemotherapies (mFOLFOX6) significantly improved objective response rate and overall survival compared to standard chemotherapy and monoclonal antibody bevacizumab. Importantly, ctDNA analysis revealed high concordance with tissue testing and demonstrated that early changes in ctDNA levels correlated with treatment response and resistance evolution.

Also, the promise of ctDNA to help refine adjuvant therapy decisions remains an active area of investigation. The DYNAMIC-III study findings previously presented at ASCO 2025 confirmed the significance of positive ctDNA, noting treatment escalation led to improved recurrence-free survival compared to standard of care in those with stage III colon cancer. The ESMO presentation of data in the ctDNA negative setting had a different conclusion. This indicates that further insight on test performance is needed before full incorporation of this test into decisions on treatment intensity and duration.

4.Regional dynamics: Monitoring Asia’s R&D rise and addressing Europe’s ongoing challenges

Regional dynamics also came into focus at ESMO, with Asia’s rising trial quality and Europe’s regulatory challenges prompting calls for global harmonisation.

Several studies conducted exclusively in China were featured in ESMO Presidential Symposia, reflecting the region’s growing footprint in global oncology innovation, especially in ADCs, bispecific antibodies, and KRAS-targeted therapies. This includes results from the RC48-C016 Phase III trial showing that the ADC disitamab vedotin combined with toripalimab, a PD-1 inhibitor, significantly outperformed chemotherapy as a first-line treatment for HER2-expressing advanced urothelial carcinoma, with superior progression-free survival (13.1 months vs. 6.5 months). According to the clinical trial sponsor, it was the first time clinical research by a China-based study team in the field of urological oncology was selected to present in the ESMO Congress Presidential Symposium.

From this expanding body of research out of Asia, questions remain about how these outcomes may be applicable across geographies and non-Asian populations globally. Experts at ESMO noted the value of further exploration by sponsors and regulators to account for regional differences in genetics, healthcare infrastructure, and trial design.

This is especially critical because, for the past decade, Europe has worked to address the ongoing challenges of maintaining R&D competitiveness as the use of trial sites in Asia and Australia increased. The impact of regulatory updates, such as the Joint Clinical Assessment requirements for all new oncology drugs submitted for registration by the European Medicines Agency, alongside overworked trial sites and lengthier contracting timelines have contributed to a decline in trial activity. Discussions at ESMO highlighted the need for streamlined processes and greater investment in infrastructure to reverse this trend.

5.Where science must meet strategy: R&D implications

The layers of scientific advances showcased at ESMO can only be useful if the real implications are accounted for within clinical trial design and planning. As operational complexity increases, so does the need for strategic planning that balances innovation with efficiency — making every trial decision count toward meaningful, patient-centric outcomes.

In a “do more with less” R&D environment, biotech sponsor segments tend to focus strongly on spending and resource allocation. As such, biotech and pharmaceutical sponsors need to thoroughly reassess control arms, endpoints, and sequencing strategies to ensure their investigational therapies remain competitive. This includes designing trials that benchmark against new standards, like T-DXd; incorporating molecular profiling earlier in the protocol; and adopting adaptive designs that respond to biomarker-driven insights, which help refine patient stratification. Similarly, drug developers should assess studies that do not meet primary endpoints to learn whether there are potential pathways to overcome challenges or redirect resources and investments. Combination strategies, resistance mechanisms, and differentiated toxicity profiles are becoming central to oncology trial planning.

A convergence of science, strategy, and patient-centric thinking

Global oncology gatherings like ESMO are meant to provide stakeholders with data outcomes that confirm new, potentially practice-changing therapies, identify those regimens not recommended due to limited efficacy or an inappropriate risk/benefit balance, optimise the use of available treatments and generate new plausible hypotheses for further exploration based on new mechanisms of action or novel combinations. All the above was accomplished at ESMO 2025, which demonstrates that oncology is entering a new era. This is defined by more earlier intervention options, fine-tuning molecular precision, and a stronger need for global R&D perspectives and updates.

With the field evolving rapidly, the challenge is to translate insights into clinical practice and to optimise trial design and regulatory frameworks that prioritise patient outcomes. As ESMO President André stated in his opening address, “The pace of change in oncology demands more than reflection; it calls for renewal.” The cancer care bar is rising and, as seen at ESMO 2025, the oncology community is ready to meet it.

About the authors

John Cochran is chief medical officer at IQVIA Laboratories. He is responsible for global medical oversight of all clinical testing where results drive patient selection and treatment in the context of clinical trials. Cochran has an extensive background as a practicing pathologist for more than two decades, having founded his own practice. He has performed numerous laboratory inspections on behalf of both The Joint Commission, as well as the College of American Pathologists, of which he is a Fellow.

José Luis García is senior medical strategy director of the Oncology Center of Excellence at IQVIA. Bringing more than 15 years of clinical oncology experience and nearly two decades in cancer research to his current role at IQVIA, García is currently responsible for overseeing the development of innovative and evidence-driven delivery strategies and solutions for oncology trial programmes, with a specialised focus on brain tumour, liver tumour, gastrointestinal, and melanoma studies. Alongside having extensive clinical experience in medical oncology and related patient care, García has served as principal investigator for various clinical and translational phase 1-4 oncology studies and has supported new and expanded existing drug life cycles through his work in medical affairs in the pharmaceutical industry.

Gijsbert Veerman is chief operating officer at IQVIA Biotech. Gijsbert oversees global project teams, investigator site services, and therapeutic divisions. With more than 27 years of clinical research experience in the CRO environment and seven years in pre-clinical oncology research, he brings a wealth of strategy and operational expertise to his role. Since joining IQVIA in 2022 as vice president and global therapeutic area head for oncology, he has contributed early and late phase oncology drug development expertise, offering strategic and study design insights to emerging biopharma and biotech customers. Gijsbert’s experience spans early phase studies, including first-in-human trials, as well as late phase drug development and biosimilars.