The European Society for Medical Oncology (ESMO) Annual Congress 2025 in Berlin highlighted significant advancements in oncology, reflecting a growing integration of technology and biology. This year’s event showcased the evolving landscape where artificial intelligence (AI) meets immunotherapy, and precision medicine blends with novel drug modalities.
Key themes included the integration of AI into clinical workflows, the expansion of targeted therapies into earlier treatment stages, and innovations in immuno-oncology beyond checkpoint inhibitors. The congress underscored a field rapidly shifting toward personalization, data-driven decision-making, and the pursuit of lasting outcomes.
Artificial intelligence is transitioning from a theoretical concept to a practical tool in oncology. Presentations highlighted AI-based imaging biomarkers revolutionizing radiology and pathology. Technologies such as Google’s Med-Gemini and Alpaca demonstrated high accuracy in whole-slide imaging, while models like SMMILe advanced the interpretation of tumor microenvironments. However, implementation challenges persist, with only about 5% of pathology labs in Switzerland—and similar rates across Europe—fully digitized. The high costs of upgrading laboratory systems remain a significant barrier. Despite this, AI agents for multi-omic modeling and computational companion diagnostics are emerging, with studies like CREATE demonstrating the potential to integrate imaging, genomics, and clinical data into cohesive decision-making frameworks. An AI-driven chest X-ray tool achieved 96% lung cancer detection, including early-stage cases among non-smokers, suggesting AI’s promise in expanding precision oncology access, especially in resource-limited settings.
Antibody–drug conjugates (ADCs) continued their evolution, moving from metastatic to early-stage disease treatment. AstraZeneca’s DESTINY-Breast05 and DESTINY-Breast11 trials revealed trastuzumab deruxtecan (T-DXd) delivering high efficacy in high-risk HER2-positive early breast cancer, with pathologic complete response rates nearing 67% and favorable invasive disease-free survival compared to trastuzumab emtansine (T-DM1). Safety concerns centered on interstitial lung disease, occurring in about 9.6% of patients but mostly mild and reversible, while cardiac toxicity remained low. Ongoing discussions focus on the optimal sequencing of T-DXd, particularly its use before or after surgery. ADCs also showed promise in bladder cancer, with the KEYNOTE-905 study reporting significant benefits for perioperative enfortumab vedotin plus pembrolizumab in cisplatin-ineligible muscle-invasive disease. These developments indicate a shift of ADCs from salvage treatments to potentially curative therapies across cancer types.
Immunotherapy beyond PD-1 inhibitors addressed resistance challenges with innovative approaches. Arenavirus-based immunotherapy (Abalos Therapeutics) demonstrated complete remissions in preclinical models and is approaching first-in-human trials. GDF-15 blockade using visugromab (CatalYm) restored PD-1 inhibitor sensitivity in refractory tumors and alleviated cancer cachexia, showing durable responses in non-small cell lung and urothelial cancers. Decoy-resistant IL-18 agonists (Simcha Therapeutics) enhanced bispecific T-cell engager efficacy, targeting inherent T-cell limitations. Oncolytic virus therapies (Transgene/BioInvent) combined with pembrolizumab induced tumor regression in both local and distant sites. These strategies highlight a new phase in immuno-oncology focused on combination treatments and novel immune modulators to overcome resistance and broaden patient benefit.
Radioligand and alpha therapies also featured prominently, with AdvanCell’s Lead-212-based PSMA-targeted alpha therapy (ADVC001) showing encouraging safety and efficacy in metastatic prostate cancer—the first clinical validation of this approach. Novartis’ Pluvicto expanded into hormone-sensitive prostate cancer, reducing progression risk by 28% when added to standard care. These innovations demonstrate targeted radiotherapy’s growing role in earlier lines, offering potent local cytotoxicity with manageable toxicities.
Metabolic targeting emerged as a promising therapeutic approach. Faeth Therapeutics’ Phase 2 DICE trial revealed that sapanisertib combined with paclitaxel reduced progression risk by 34% and extended progression-free survival by 45% in platinum-resistant ovarian cancer. The drug’s multi-node inhibition of PI3K, mTORC1, and mTORC2 addresses metabolic plasticity, a major driver of resistance. This approach suggests metabolic targeting may become a fundamental pillar alongside immunotherapy and ADCs, especially in tumors linked to obesity and metabolic disorders.
Precision oncology advanced with the growing use of circulating tumor DNA (ctDNA) to guide treatment. Trials including DYNAMIC-III in stage III colon cancer and IMvigor011 in urothelial cancer confirmed ctDNA’s value as a prognostic biomarker and a tool to de-escalate therapy, enabling patients with negative post-surgery ctDNA to avoid intensive chemotherapy without compromising outcomes. This molecularly guided approach signals a shift toward personalized adjuvant treatment, aligning intervention intensity with individual risk.
New targets and modalities gained attention, including KRAS G12D inhibition by Incyte’s INCB161734, which achieved overall response rates of up to 34% in heavily pretreated pancreatic cancer—a notable breakthrough for this historically elusive mutation. Bispecific antibodies such as INCA33890 targeting TGFβR2 and PD-1 showed activity in microsatellite stable colorectal cancer, a group traditionally resistant to immunotherapy. Next-generation ADCs from Tubulis demonstrated a 59% response rate in platinum-resistant ovarian cancer without biomarker selection, validating new targets and technology platforms.
Large pharmaceutical and biotech companies showcased robust pipelines. AstraZeneca expanded its ADC portfolio, including approaches for triple-negative breast cancer, and strengthened its HER2 strategies. Ipsen acquired ImCheck Therapeutics for €350 million, focusing on BTN3A-targeted immunotherapy in acute myeloid leukemia. Arcus reported a median overall survival of 26.7 months with domvanalimab plus zimberelimab in gastric cancer, supporting TIGIT as a next-generation checkpoint target. Merck, Exelixis, and others advanced ADCs, kinase inhibitors, and immuno-oncology combinations addressing unmet needs.
ESMO 2025 underscored three key imperatives for the future of oncology: the integration of technology and biology, with AI and multi-omics guiding decision-making; diversification of therapeutic modalities beyond chemotherapy and checkpoint inhibition to include ADCs, radioligands, metabolic inhibitors, and immune modulators; and personalization at scale, using ctDNA and biomarkers to tailor treatment intensity, improve outcomes, and reduce toxicity and cost.
As these innovations transition from research to clinical practice, challenges remain in implementation, access, affordability, and equity. For clinicians, regulators, and industry, the message from Berlin is clear: the future of cancer care is targeted, integrated, intelligent, and transformative.
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