The future of oncology is adaptive: What ESMO 2026 revealed about cancer's next chapter

Identifying the right molecular target and matching it with the right therapy is the longstanding treatment model that transformed cancer care. However, at the European Society for Medical Oncology 2026 Congress, one of oncology's largest global gatherings of researchers, clinicians, and industry leaders, a shift in thinking became apparent. As targeted therapies become more effective and cancer treatment options continue to expand, the future of oncology may depend as much on adapting to evolving disease biology as it does on identifying the right target in the first place.

Across tumour types, three developments repeatedly surfaced throughout the congress, each reflecting a notable transition in how cancer is being managed. Researchers are focusing on better ways to monitor biological change, design sophisticated strategies to intervene against multiple drivers of diseases in parallel, and develop new approaches to anticipate resistance before it limits patient benefit. Together, these updates point toward what may become the next chapter of oncology innovation—adaptive precision oncology.

Monitor: No longer measuring cancer at a single point in time

Several presentations at ESMO reinforced the value of understanding how tumours adapt after treatment begins and how clinical strategies can evolve in response. Studies evaluating resistance following epidermal growth factor receptor-targeted therapy in patients with EGFR-mutated non-small cell lung cancer indicated the growing role of reassessing patients after progression, rather than relying solely on molecular information collected at diagnosis.

As tumours evolve under treatment pressure, new resistance pathways can emerge. Repeated molecular testing can help identify these changes and inform treatment adaptation. In particular, findings from the SAFFRON Phase III study illustrated how identifying MET-driven resistance, a molecular escape pathway that can emerge following EGFR-targeted therapy, may uncover newly actionable biology and help guide subsequent treatment decisions.

More generally, the DeLLphi-305 Phase III study provides a clinical precedent supporting the potential value of introducing effective therapy earlier in the disease course, with positive results from adding tarlatamab to durvalumab during first-line maintenance in SCLC. While not direct evidence for molecularly guided pre-progression treatment, these findings support a broader hypothesis applicable across tumour types: could emerging resistance mechanisms be detected and targeted before clinical or radiological progression? In EGFR-mutant NSCLC, longitudinal molecular monitoring could potentially identify emerging MET or other actionable alterations and guide earlier treatment adaptation. This paradigm may extend to other molecularly defined tumours, but will require prospective validation of the optimal timing, actionable signals, and clinical benefit.

This evolution is helping expand the role of circulating tumour DNA, serial molecular profiling, and repeat tissue assessment. While ctDNA has often been discussed as a tool for patient selection and biomarker-enriched trial design, ESMO indicated a broader future. Increasingly, these technologies are being viewed as mechanisms for monitoring disease evolution, identifying emerging resistance, detecting minimal residual disease, and supporting treatment decisions throughout the patient journey. The next challenge will be determining whether earlier detection of molecular resistance can be translated into meaningful clinical benefit through biomarker-guided intervention before radiographic progression becomes apparent. Such approaches would represent an important evolution for adaptive precision oncology, shifting the focus from detecting resistance to actively intercepting it.

Looking further ahead, the Phase III INTerpath-001 study, widely viewed as a potentially paradigm-changing milestone for individualised mRNA neoantigen cancer vaccines, hints at a more dynamic future. Advances in longitudinal molecular monitoring may create opportunities to pair evolving biological information with increasingly personalised therapeutic approaches, enabling treatment strategies to adapt alongside changes in tumour biology.

Intervene: No longer addressing cancer through a singular mechanism

If monitoring represents the first signal of adaptive precision oncology, the second is the emergence of therapies designed to respond to increasingly complex and evolving disease biology. Across the ESMO 2026 Congress, some of the most closely watched studies featured next-generation ADCs, bispecific antibodies, multispecific immunotherapies, and T-cell engagers. Instead of focusing on a single molecular driver, these approaches seek to address multiple biological pathways simultaneously. This reflects a growing recognition that effective treatment may require addressing multiple drivers of disease at once, including tumour diversity, resistance development, and the ways cancers avoid immune attack.

ADCs provide a useful example of how therapeutic intervention is evolving. While early ADC development focused on establishing clinical activity, current research is increasingly exploring how these agents can be deployed in biologically complex settings characterised by treatment resistance, evolving disease biology, and growing therapeutic competition.

Phase III studies PANKU-Lung01 and HERON-Lung01 show how therapeutic intervention is evolving in response to increasingly complex treatment landscapes. Both trials enrolled patients with EGFR-mutated NSCLC whose disease had progressed after EGFR-tyrosine kinase inhibitor osimertinib, a setting characterised by diverse resistance mechanisms and historically limited options beyond platinum chemotherapy. Rather than introducing another single-target approach, these studies evaluated next-generation ADCs designed to deliver more precise and differentiated treatment following targeted therapy failure. The positive results seen with the EGFR×HER3 bispecific ADC izalontamab brengitecan in PANKU-Lung01 and the HER3-directed ADC ruzaltatug rezetecan in HERON-Lung01 highlight how treatment development is increasingly being shaped by an understanding of resistance biology, creating opportunities for more tailored intervention strategies as disease evolves.

These findings also point to a key question: can treatment outcomes be improved not only through better therapies, but by intervening at more biologically advantageous points in the disease course? Recent findings suggest that when and how therapies are introduced may be as important as the mechanism itself. DeLLphi-305 showed the potential value of intervening during disease control, rather than waiting for clinical relapse. A similar principle may emerge with multispecific approaches. Despite historically limited activity from broad transforming growth factor-beta targeting in pretreated colorectal cancer, improved understanding of molecular and microenvironmental heterogeneity is enabling more biologically integrated strategies. At ESMO Congress 2026, TGF-βR2 × PD-1 bispecific antibody INCA33890 combined with FOLFOX-bevacizumab, achieved a 71.4% objective response rate in a first-line cohort of patients with microsatellite-stable colorectal cancer (abstract 1954O), a tumour type that has historically demonstrated limited responsiveness to immunotherapy. Although these findings remain preliminary, it is worth exploring if improved biological selection, simultaneous targeting of complementary pathways, and earlier intervention could unlock therapeutic benefit that may otherwise be missed in heavily pretreated disease.

The use of T-cell engagers continues to expand beyond their initial applications, with growing interest across solid tumours and earlier treatment settings. PRAME-directed immune therapies, which target an antigen expressed across multiple solid tumours, but with limited expression in healthy adult tissue, was one application discussed at ESMO. The Phase I/II study of IMA402, a T-cell engager, demonstrated a confirmed objective response rate (ORR) of 25% and a disease control rate of 63% among efficacy-evaluable patients with heavily pretreated advanced solid tumours (abstract 1955RO). T-cell receptor-based cell therapy IMA203CD8 achieved a confirmed ORR of 41% in heavily pretreated patients with PRAME-positive solid tumours, including melanoma, synovial sarcoma, ovarian cancer, and uterine cancer (abstract 1946O). Notably, the longest reported response exceeded three years, highlighting the potential for durable benefit. These studies show growing momentum behind engineered immune approaches that actively redirect T-cells against cancer and expand the reach of cellular immunotherapy beyond haematologic malignancies.

Anticipate: No longer defining cancer by the initial response

The final signal of adaptive precision cancer care emerging from ESMO 2026 was the extent to which resistance is more often being treated as an anticipated phase of disease management, instead of an unexpected setback.

The first era of precision medicine often focused on generating responses. The next may focus on sustaining them. For example, in gastrointestinal stromal tumours (GIST), drug developers are increasingly designing therapies around the expectation of resistance, rather than viewing it as a late-stage challenge. KIT is the primary cancer-driving protein in most of these tumours, and secondary KIT mutations are a common cause of treatment resistance. In the PEAK Phase III study (abstract 3717RO), a combination of bezuclastinib, a selective inhibitor of mutant KIT signalling, and sunitinib, a multi-targeted tyrosine kinase inhibitor, showed activity across heterogeneous KIT-resistant clones. Following crossover after sunitinib progression, median progression-free survival was 7.4 months, and objective response rate was 29.7%. Among patients whose disease had continued to progress on sunitinib alone, 56% responded after the addition of bezuclastinib. These findings suggest a future in which resistance is not only managed after it occurs, but anticipated and targeted as part of treatment strategy from the outset.

Together, the PEAK and INCA33890 studies raise the possibility that deeper biological understanding may enable more effective use of complementary interventions earlier in the disease course, before individual resistance pathways become dominant drivers of progression.

Adaptive precision oncology: Potentially defining oncology’s next steps

The strongest development emerging from ESMO 2026 may not have been any single study or therapeutic modality. Rather, it was a progression in how the oncology community is approaching disease management.

For years, oncology focused on identifying the right target and selecting the right therapy. Today, a growing body of evidence suggests that success will also depend on the ability to monitor disease continuously, intervene through multiple biological mechanisms, and anticipate resistance before it emerges. In that sense, the future of oncology may depend less on precision at a single moment in time and more on precision across the entire disease journey.

Where precision medicine helped identify the right patients, adaptive precision may determine how we in the oncology community care for them in the years ahead.

About the authors

Dr David Alsadius, PhD, senior medical director at the Oncology Center of Excellence, IQVIA, is a board-certified clinical oncologist with more than 20 years of oncology experience in both industry and academia. In his current role, Dr Alsadius advises pharmaceutical and biotechnology companies on the development of oncology products.

José Luis García is senior medical strategy director at the Oncology Center of Excellence, IQVIA. He brings more than 16 years of clinical oncology experience and nearly two decades in cancer research to his current role. 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 I-IV oncology studies and has supported new and expanded existing drug life cycles through his work in medical affairs in the pharmaceutical industry.