The European Society for Medical Oncology (ESMO) Annual Congress 2025, held in Berlin, highlighted significant advancements in oncology, emphasizing the integration of technology and biology. Key themes included the use of artificial intelligence (AI) in clinical workflows, expansion of targeted therapies to earlier disease stages, and innovations in immuno-oncology beyond checkpoint inhibitors.
Artificial intelligence has progressed from a conceptual tool to practical application in oncology. Sessions demonstrated how AI-based imaging biomarkers are transforming radiology and pathology, with platforms like Google’s Med-Gemini and Alpaca showing high accuracy in whole-slide imaging. Spatial models such as SMMILe enable detailed interpretation of tumor microenvironments. However, challenges remain in digitizing pathology labs, with only about 5% of Swiss labs fully digital, reflecting broader European trends. Upgrading infrastructure involves significant costs, estimated at €5 million per site. Emerging AI agents aim to integrate imaging, genomics, and clinical data into unified decision-making tools. The CREATE study, conducted by Qure.ai and AstraZeneca, showcased an AI-driven chest X-ray tool identifying 96% of lung cancer cases, including early-stage disease in non-smokers, signaling AI’s potential to democratize precision oncology.
Antibody–drug conjugates (ADCs) continue to revolutionize cancer treatment, moving from metastatic settings into early disease. AstraZeneca’s DESTINY-Breast05 and DESTINY-Breast11 trials demonstrated that trastuzumab deruxtecan (T-DXd) achieved pathologic complete response rates near 67% in high-risk HER2-positive early breast cancer and showed superior invasive disease-free survival compared to trastuzumab emtansine (T-DM1). Safety concerns include interstitial lung disease occurring in about 9.6% of patients, mostly mild and reversible, with low cardiac toxicity. Debates continue on optimal sequencing, with a general preference for post-operative administration following neoadjuvant therapy. ADCs are also reshaping bladder cancer treatment, as evidenced by KEYNOTE-905 results showing significant benefits of perioperative enfortumab vedotin combined with pembrolizumab in cisplatin-ineligible muscle-invasive disease, marking a shift toward curative intent.
Immunotherapy is evolving beyond PD-1 checkpoint inhibition, addressing resistance through novel approaches. Arenavirus-based immunotherapy ABX-001 from Abalos Therapeutics activates systemic immunity and is entering first-in-human trials after promising preclinical complete remissions. CatalYm’s visugromab, a GDF-15 blocker, restored PD-1 inhibitor sensitivity in refractory tumors, delivering durable responses over 32 months in non-small cell lung and urothelial cancers, while also mitigating cancer cachexia. Simcha Therapeutics introduced ST-067, a decoy-resistant IL-18, enhancing bispecific T-cell engager efficacy. Oncolytic virus therapy combining BT-001 with pembrolizumab demonstrated tumor shrinkage in injected and distant lesions, reinforcing the potential of multifunctional viral platforms. The future of immunotherapy will focus on combination strategies and novel immune modulators to overcome resistance.
Radioligand and alpha therapies also featured prominently. AdvanCell’s ADVC001, a PSMA-targeted Lead-212-based alpha therapy, showed encouraging safety and efficacy in metastatic prostate cancer, marking the first clinical validation of this approach. Novartis’ Pluvicto expanded into hormone-sensitive disease, reducing progression risk by 28% when added to standard treatment. These advances highlight the increasing role of targeted radiotherapy in earlier treatment lines, offering potent, localized cytotoxicity with manageable toxicities.
Targeting cancer metabolism emerged as a promising therapeutic strategy. Faeth Therapeutics’ Phase 2 DICE trial in platinum-resistant ovarian cancer showed a 34% reduction in progression risk and 45% extension in progression-free survival when combining sapanisertib with paclitaxel. This multi-node inhibitor targets PI3K, mTORC1, and mTORC2, addressing metabolic plasticity associated with resistance. Metabolic targeting is poised to become a foundational pillar alongside immunotherapy and ADCs, especially in tumors linked to obesity and metabolic disorders.
Precision oncology advanced with circulating tumor DNA (ctDNA) guiding treatment decisions. The DYNAMIC-III trial in stage III colon cancer and IMvigor011 in urothelial cancer validated ctDNA as a prognostic marker for minimal residual disease. Patients negative for ctDNA after surgery achieved favorable outcomes without intensive chemotherapy, reducing toxicity and healthcare costs. This approach signals a shift toward molecularly informed adjuvant therapy.
Emerging targets at ESMO 2025 included KRAS G12D inhibition with Incyte’s INCB161734, showing overall response rates up to 34% in heavily pretreated pancreatic cancer. Bispecific antibodies like INCA33890, targeting TGFβR2 and PD-1, achieved responses in microsatellite stable colorectal cancer, traditionally resistant to immunotherapy. Next-generation ADCs from Tubulis demonstrated a 59% overall response rate in platinum-resistant ovarian cancer without biomarker selection, validating NaPi2b as a novel target.
Pharmaceutical companies highlighted robust pipelines. AstraZeneca expanded its ADC portfolio with TROPION-Breast02 in triple-negative breast cancer and strengthened HER2 programs. 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 critical needs.
ESMO 2025 underscored three key imperatives for oncology’s future: integrating technology and biology through AI and multi-omics; diversifying therapeutic modalities beyond chemotherapy and checkpoint inhibitors to include ADCs, radioligands, metabolic inhibitors, and novel immune modulators; and scaling personalization through ctDNA-guided strategies and biomarker-driven trials to match treatment intensity with individual risk.
As these innovations transition from research to clinical practice, challenges remain in implementation, ensuring access, affordability, and equity. The congress conveyed a clear message: the future of cancer care will be targeted, integrated, intelligent, and transformative.
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