The 2026 European Society for Medical Oncology (ESMO) Congress once again brought together the international oncology community to explore the latest advances in cancer research and treatment.
Our team spent the week in Madrid, introducing new solutions and presenting research of our own. We came away impressed by the breadth and quality of this year’s program, and particularly by how it encouraged the oncology community to look beyond individual advances and consider the bigger picture. We expected compelling results from highly anticipated clinical trials investigating novel combination therapies and innovative ways to harness the immune system, and there was no shortage of those. But we were equally struck by the attention given to efforts to reduce the burden of treatment and adapt therapeutic strategies as cancer evolves.
Taken together, these discussions pointed to a broader shift in oncology: toward more personalized, adaptive and sustainable approaches to cancer care. Realizing that promise will require not only continued innovation in clinical research, but also a clearer understanding of how new approaches are likely to perform across diverse patient populations and healthcare systems.
Here are our three top takeaways from this year's congress.
Takeaway #1: A new generation of cancer therapies is reimagining how we attack tumors
A new wave of cancer therapies is expanding the ways researchers can harness the immune system and target tumor cells. At ESMO 2026, this was evident in the diversity of approaches under investigation, from personalized cancer vaccines and novel T cell therapies to bispecific antibodies and increasingly sophisticated treatment combinations.
One notable example was the phase 3 INTerpath-001 trial in melanoma. Building on the promise of mRNA technology, researchers found that intismeran autogene, a personalized mRNA cancer vaccine, combined with pembrolizumab reduced the risk of recurrence or death by 42% compared with pembrolizumab alone in patients with resectable melanoma — a long-awaited breakthrough and major landmark for cancer vaccines.
Another important development came from DeLLphi-305, a phase 3 trial in extensive-stage small cell lung cancer. Combining tarlatamab (a bispecific T cell engager targeting DLL3-expressing tumor cells) with durvalumab as first-line maintenance therapy extended median overall survival from 12.7 to 21.1 months and median progression-free survival from 1.9 to 7.4 months compared with durvalumab alone — demonstrating the potential of bringing new immune-engaging mechanisms into earlier stages of treatment.
Researchers also presented new combinations targeting complementary mechanisms of action. The phase 3 HARMONi-GI1 study evaluated the PD-1/VEGF-targeting bispecific antibody ivonescimab with chemotherapy in advanced biliary tract cancer, while the phase 3 VOLGA trial investigated durvalumab alongside the antibody-drug conjugate (ADC) enfortumab vedotin in muscle-invasive bladder cancer.
These studies illustrate how oncology research is moving beyond individual therapeutic targets toward more sophisticated strategies that activate, redirect and amplify the immune response, often in combination with complementary treatment mechanisms.
Takeaway #2: Treatment optimization is putting quality of life and access in the spotlight
In line with ESMO’s Roadmap 2030 initiative, another prominent theme at ESMO 2026 was improving the experience of cancer treatment, not just extending survival. Researchers explored ways to preserve organ function, reduce toxicity and simplify treatment delivery while maintaining efficacy.
The phase 2 AZUR-1 trial illustrated the potential to preserve organ function in patients with previously untreated, locally advanced mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) rectal cancer. Instead of proceeding directly to chemotherapy, radiation and surgery, patients received nine cycles of dostarlimab, an anti-PD1 antibody, with those achieving a complete clinical response eligible for nonoperative management. Among patients with at least 12 months of follow-up, 68% sustained their complete clinical response by investigator assessment, and 76% achieved this with dostarlimab alone, pointing to the potential to spare some patients the toxicity and morbidity of conventional surgical treatment.
In a similar theme of testing de-escalation, phase 3 PRABITAS trial addressed treatment burden by comparing a simplified 14-day and conventional 28-day schedule of trifluridine/tipiracil plus bevacizumab in refractory metastatic colorectal cancer. The shorter schedule was noninferior for overall survival (11.3 versus 10.3 months) and reduced grade 3 or higher neutropenia from 39% to 13%, suggesting that treatment delivery can be optimized without compromising survival.
However, reducing treatment intensity requires careful evaluation. The phase 3 MOIO trial investigated whether patients with advanced or metastatic solid tumors who had responded to six months of immunotherapy could continue treatment at 12-week intervals rather than the standard schedule. The trial was stopped early on the data monitoring committee's recommendation after overall survival signals favored standard dosing, and non-inferiority for progression-free survival was not shown. Notably, the less frequent dosing offered no meaningful safety advantage. Given the early stop, no firm conclusions can be drawn.
Takeaway #3: Adapting treatment as cancer evolves
Precision oncology has traditionally focused on identifying the molecular alterations that make a tumor susceptible to a particular treatment. At ESMO 2026, research highlighted a broader ambition: understanding how tumors evolve under treatment pressure, why resistance develops, and how therapeutic strategies should adapt as the disease changes.
Antibody-drug conjugates (ADCs) offer one illustration of this shift. As these therapies expand across tumor types, researchers are looking beyond the identification of targetable antigens to investigate why some patients respond while others develop resistance. Variations in target expression, tumor heterogeneity and differences in payload sensitivity can all influence treatment effectiveness. Understanding these mechanisms will be critical to optimizing ADC development and identifying the best treatment sequences.
The phase 3 SAFFRON trial provided a compelling clinical example of targeting acquired resistance. In patients with EGFR-mutated advanced non-small cell lung cancer (aNSCLC) whose disease had progressed on osimertinib, combining osimertinib with savolitinib to overcome MET-mediated resistance to anti-EGFR therapy improved progression-free and overall survival compared to platinum-based chemotherapy.
Liquid biopsies and circulating tumor DNA (ctDNA) are also creating opportunities to adapt treatment decisions to tumor evolution. The phase 2 PACE-LUNG study explored whether early molecular response could help identify patients with EGFR-mutated aNSCLC who might benefit from treatment intensification. Patients with detectable EGFR-mutant ctDNA after three weeks of first-line osimertinib received additional chemotherapy. The approach demonstrated feasibility and encouraging outcomes, although controlled studies are needed to establish its clinical benefit.
Finally, the updated ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT v2), released just prior to the meeting, reflects the growing importance of interpreting molecular findings in their clinical context. Alongside a more granular assessment of actionable alterations, the framework introduces a dedicated classification for resistance biomarkers, recognizing that understanding the mutations driving resistance can be as important as identifying those that predict treatment benefit.
A common denominator: Connecting clinical advances with real-world evidence
Across these three areas of innovation, advances in cancer treatment are creating new opportunities, but also new questions about which patients are most likely to benefit, how to optimize treatment, and how to adapt care as diseases evolve. High-quality real-world evidence (RWE) can help answer these questions, complementing clinical trial findings with insights from routine oncology practice.
- For emerging therapies, multimodal datasets can help characterize biomarker prevalence, identify molecular subgroups, and assess treatment outcomes across broader patient populations — including international markets like the UK, Germany, and Japan where Flatiron’s new breast cancer and NSCLC Panoramic datasets can be used to support local, regional, and global studies.
- For treatment optimization, longitudinal RWE can provide a broader perspective on the balance between effectiveness, safety and treatment burden. Using a comprehensive and intuitive platform like Flatiron Telescope, researchers can quickly examine treatment duration, dose modifications, and more to understand how treatment strategies perform in routine practice and where opportunities exist to improve patient experience and access to care.
- Finally, as precision oncology becomes more dynamic, linking molecular profiles with longitudinal treatment histories and outcomes can help identify resistance patterns, evaluate treatment sequencing and understand how molecular testing, including ctDNA, informs clinical decisions in practice. These insights can help researchers identify opportunities to adapt treatment as tumor biology changes.
ESMO 2026 showcased its share of landmark advances, but it also underscored the broader implications of a rapidly evolving oncology landscape for patients, clinicians, and health systems worldwide. A robust RWE foundation is essential for clinicians, academic researchers, and biopharma companies to bridge the gap between therapeutic innovation and the realities of cancer care today.
