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Highlights from ESMO 2025

Written by Elin Siddall, SVP Medical & Scientific Services on Thursday, November 6, 2025

A summary of the most pertinent oncology data and insights presented at this year’s ESMO conference

ESMO 2025 concluded last week in Berlin, marking the 50th anniversary of this important oncology congress. Once again, a packed and stellar scientific program did not disappoint, with ADCs continuing to deliver and expand on their promise in established and emerging tumor types, while other topics such as bispecific antibodies, ctDNA technology, and digital innovation also garnered attention.

This summary highlights some of the key practice-confirming as well as potentially practice-changing datasets presented at ESMO 2025,* along with areas of focus beyond the therapeutics that also have the promise to shape the future of oncology.

*Unless otherwise stated, data discussed within this summary are from Phase 3 clinical trials.

Bladder cancer

Once again, bladder cancer data hit the headlines for the right reasons at ESMO 2025, with presentations in this field included in each Presidential Symposium.

First up were data from the KEYNOTE-905/EV-303 trial in cisplatin-ineligible MIBC, which demonstrated significant and clinically meaningful improvements in EFS, OS, and pCR in patients receiving peri-operative EV+P vs control group patients.1 Results from the IMvigor011 study showed that ctDNA can be used to identify MRD in patients with MIBC and guide decision-making around the use of adjuvant immunotherapy. This underpins the promise of ctDNA to direct treatment to those who need it and spare those who will not benefit.2 In la/mUC, data showed that a HER2-targeting ADC + IO combination therapy of DV+T outperformed chemotherapy in HER2-expressing tumors, with statistically significant improvements in mPFS, OS, and pCR.3 Nevertheless, despite the high potential for these positive outcomes to change clinical practice, questions emerged, including around the optimal sequencing of treatments and the availability of robust biomarker testing for all patients.

Elsewhere, the final analysis from the POTOMAC trial confirmed the significant and clinically meaningful improvement in DFS observed from the addition of durvalumab to induction and maintenance BCG (vs BCG alone) with a manageable safety profile. These data support durvalumab + BCG as a new treatment option in BCG-naïve, high-risk NMIBC.4

Prostate cancer

For prostate cancer, final data from the EMBARK trial confirmed previously reported MFS and demonstrated a significant OS benefit from the addition of enzalutamide to leuprolide (vs leuprolide), thus supporting the use of the combination as SOC in high-risk, biochemically recurrent prostate cancer.5

In mHSPC, data from the PSMAddition trial showed that the addition of 177Lu-PSMA-617 to doublet treatment of ADT plus an ARPI for PSMA-positive disease demonstrated significantly improved rPFS, including across all subgroups. However, OS data are still immature, and it was reflected that demonstration of an OS benefit may not be possible because of the cross-over nature of the trial. Furthermore, with poorer QoL outcomes observed vs the doublet SOC, it is unclear whether there is a broad role for this novel triplet combination in this setting.6 Data from CAPItello-281 highlighted the potential of an emerging biomarker-driven treatment in de novo PTEN-deficient mHSPC, with significant improvements in rPFS observed with the addition of capivasertib to AA* + ADT (vs AA* + ADT + placebo).7 Finally, PROs from the AMPLITUDE trial demonstrated that, in addition to significantly improving rPFS, niraparib + AA† maintained baseline HRQoL (vs placebo + AA†) in a population with HRRm mHSPC.8 These results highlight the ever-growing potential of established and novel biomarker-driven strategies to further improve outcomes in metastatic prostate cancer. Nevertheless, the impact is somewhat diminished when contextualized with current real-world biomarker testing rates for approved treatments in some regions.

*In combination with prednisone/prednisolone; †In combination with prednisone.

RCC

Renal cell carcinoma (RCC)

In RCC, results from the RAMPART study showed that, after resection of primary RCC, adjuvant therapy with durvalumab and tremelimumab improved DFS compared with active monitoring, particularly in those at highest risk of relapse.9 Novel 1L IO-based regimens in ccRCC were explored in substudy 03A of the Phase 1/2 KEYMAKER-U03 trial, with the triplet pembrolizumab + lenvatinib + belzutifan combination showing encouraging signs, building anticipation for results from an ongoing Phase 3 study (LITESPARK-012).10 Together, these results underpin the pivotal role ICI plays in RCC — from maintenance therapy after nephrectomy, particularly in high-risk disease, to the backbone of evolving combination treatment approaches in metastatic disease.

The Phase 2 LenCabo study represents the first head-to-head study of two contemporary 2L treatment options for metastatic ccRCC after ICI therapy: lenvatinib + everolimus vs cabozantinib. Results from LenCabo were presented at ESMO – OS data are still immature; however, significantly longer mPFS was reported with the former treatment option vs the latter.11

Breast cancer

In early breast cancer, long-term data from the monarchE (7 years)12 and NATALEE (5 years)13 trials have further cemented the role of CDK4/6 inhibitors in the HR+/HER2- eBC toolbox.

Novel ADCs took a step forward to the curative setting in HER2+ eBC, with two trials exploring the possible benefits of T-DXd in high-risk residual disease in the neoadjuvant setting, either in untreated patients in DESTINY-Breast11 (T-DXd–THP vs ddAC–THP)14 or after initial neoadjuvant therapy in DESTINY-Breast05 (T-DXd vs T-DM1).15 Both trials showed statistically significant improvements in their primary endpoints (pCR and IDFS, respectively) in the T-DXd arms vs the control arms. While there was clearly excitement around the clinical benefit from T-DXd treatment in these high-risk patients, questions now arise around sequencing and when to use this new ADC in the neoadjuvant setting, likely with the use of a biomarker strategy to support decisions.

Positive data for TROP2-targeted ADCs were also prominent in metastatic breast cancer datasets. In 1L immunotherapy-ineligible mTNBC, two trials demonstrated improved outcomes in the investigative arms with TROP2 ADCs: the ASCENT-03 trial (SG vs CT) showed significantly improved mPFS,*16 and the TROPION-Breast02 trial (Dato-DXd vs CT) demonstrated significantly improved mPFS and OS.17 These results offer a potential treatment shift for these patients, while also laying the foundation for future ADC exploration in mTNBC.

*OS data remain immature.

Lung cancer

A plethora of datasets and insights were also presented for lung cancer. Looking at ALK+ NSCLC, long-term data (7 years) from the pivotal ALEX trial underpinned the use of alectinib in untreated patients with advanced disease.18 Moving to early-stage disease, the benefits of adjuvant therapy with ALK inhibitors were demonstrated in trials with ensartinib (vs placebo; post-tumor resection and adjuvant chemotherapy: ELEVATE)19 and alectinib (vs chemotherapy; post-tumor resection: ALINA).20

Findings from the Phase 2 NorthStar trial demonstrated that the addition of LCT to osimertinib in 2/3L treatment of EGFRm la/mNSCLC resulted in improved mPFS (vs osimertinib monotherapy), potentially representing another treatment option.21 In the same post-EGFR TKI setting, TROP2-targeted ADCs made another appearance in the OptiTROP-Lung04 trial, with significantly prolonged mPFS and OS observed with sac-TMT vs chemotherapy.22

Long-term OS data from the Phase 2 PHAROS trial reinforced the use of BRAF + MEK inhibitor therapy with encorafenib and binimetinib in BRAF V600E-mutant mNSCLC.23

Data from the HARMONi-6 trial investigating the PD-1/VEGF bispecific ivonescimab vs a PD-1 inhibitor in addition to chemotherapy in advanced squamous NSCLC — a subgroup of NSCLC with high unmet need — demonstrated significant improvements in mPFS across all subgroups.24 Growing excitement around novel bispecifics was seemingly justified by these promising data; however, translation into meaningful OS outcomes, as well translation across broader geographic populations, is needed.

In ES-SCLC, addition of the BiTE molecule tarlatamab to 1L chemotherapy followed by PD-L1 inhibitor maintenance therapy in the Phase 1b DeLLphi-303 study resulted in improved mPFS, with mOS not yet reached.25

Ovarian cancer

Technology

Progress in technology: Precision medicine; AI & digital

Precision medicine continues to be an area of huge academic as well as clinical interest at ESMO, with presentations spanning a spectrum of topics including access to biomarker testing, as well as the role of new and established biomarkers in treatment paradigms. Of particular interest was the potential application of ctDNA in cancer screening and in mutation detection to guide treatment decision-making. The promise of ctDNA as a non-invasive, dynamic tool for the analysis of cancer biomarkers across all stages of the patient journey was discussed in several presentations, including within a dedicated ctDNA-focused session. Although negative results from some ctDNA-guided trials highlight the need to optimize the sensitivity and feasibility of ctDNA testing,27,28 promising data in bladder and colorectal cancer suggest ctDNA could be a valuable tool for informing treatment escalation or de-escalation strategies, which could hail “a new era” in the management of early-stage disease.29,30

The ever-growing prominence and relevance of the field of “AI and digital” within oncology meant that this topic had its own scientific track for the first time at ESMO 2025. Research on the use of AI in clinical assessments (eg, pathology, imaging, and multiomic data) to determine prognostic and predictive outcomes continues to gain traction. At ESMO, four studies presented findings that underline the potential application of AI technology to help guide clinical decision-making by identifying which patients are likely to benefit from particular treatments and which should be spared unnecessary toxicities.31–34

Collectively, the data presented at ESMO on the use of progressive technologies (ctDNA, AI tools, etc.) to improve and personalize treatment pathways — for example, through identification of new therapeutic modalities, augmentation of clinical trial design and implementation, enhancement of diagnostic capabilities, and integration of adaptive treatment and management strategies based on prognostic and predictive outcomes and response to treatments — clearly demonstrates the anticipated role of technology-driven approaches as a core pillar in future oncology care. Nevertheless, presented results highlighted the need for further research and refinement, while key questions around robust validation in large prospective populations, as well as funding and reimbursement, must be addressed for broad deployment of these promising new technologies in routine clinical workflows.

In addition, the use of digital patient-centered tools for supportive care (eg, monitoring of symptoms and psychological aspects) had a positive impact on patient QoL outcomes in three studies.35–37

In the oncology landscape (as demonstrated by the presentations at ESMO) and beyond, the body of evidence for the broad adoption of digital health tools continues to expand — integration into routine care and establishing reimbursement models will be critical to their success.

Conclusion

ESMO 2025 had record-breaking attendance (37,000 attendees) and concluded with a palpable sense of excitement around practice-changing datasets in multiple tumor types, as well as the promise of new molecular entities, treatment approaches, and technologies. Nevertheless, despite the exciting trajectory of progress we are seeing, unmet needs still persist through many lenses. These include the need for breakthrough or improved therapies and treatment approaches that allow patients to live longer AND live better, as well as the need for equitable healthcare with timely access to the latest testing and treatment approaches for ALL patients.

At OPEN Health, we look forward to seeing the continued evolution of the oncology landscape, and we will be present at upcoming oncology and hemato-oncology congresses, including ASH 2025, ASCO GU 2026, and ASCO 2026, where we will be closely following the latest science as well as supporting our clients.

Get in touch if you would like to discuss the support we can provide to enhance your congress experience or if you would like to connect in person at an upcoming congress.

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1L, first line; 2L, second line; 2/3L, second or third line; AA, abiraterone acetate; ADC, antibody–drug conjugate; ADT, androgen deprivation therapy; AI, artificial intelligence; ALK, anaplastic lymphoma kinase; ARPI, androgen receptor pathway inhibitor; BCG, Bacillus Calmette–Guérin; BiTE, bispecific T-cell engager; ccRCC, clear cell renal cell carcinoma; CDK4/6, cyclin-dependent kinase 4/6; CT, chemotherapy; ctDNA, circulating tumor DNA; Dato-DXd, datopotamab deruxtecan; ddAC, dose-dense doxorubicin + cyclophosphamide; DFS, disease-free survival; DV+T, disitamab vedotin + toripalimab; eBC, early breast cancer; EFS, event-free survival; EGFRm, epidermal growth factor receptor-mutated; ES-SCLC, extensive-stage small cell lung cancer; EV+P, enfortumab vedotin + pembrolizumab; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; HRQoL, health-related quality of life; HRRm, homologous recombination repair mutated; ICI, immune checkpoint inhibition; IDFS, invasive disease-free survival; IO, immuno-oncology; la/mNSCLC, locally advanced or metastatic non-small cell lung cancer; la/mUC, locally advanced or metastatic urothelial carcinoma; LCT, local consolidative therapy; MEK, mitogen-activated extracellular signal-regulated kinase; MFS, metastasis-free survival; mHSPC, metastatic hormone-sensitive prostate cancer; MIBC, muscle-invasive bladder cancer; mNSCLC, metastatic non-small cell lung cancer; mOS, median overall survival; mPFS, median progression-free survival; MRD, molecular residual disease; mTNBC, metastatic triple-negative breast cancer; NMIBC, non-muscle-invasive bladder cancer; NSCLC, non-small cell lung cancer; OS, overall survival; pCR, pathologic complete response; PD-1, programmed cell death protein 1; PFS, progression-free survival; PRO, patient-reported outcome; PROC, platinum-resistant ovarian cancer; PSMA, prostate-specific membrane antigen; PTEN, phosphatase and tensin homolog deleted on chromosome 10; QoL, quality of life; RCC, renal cell carcinoma; rPFS, radiographic progression-free survival; sac-TMT, sacituzumab tirumotecan; SG, sacituzumab govitecan; SOC, standard of care; T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan; THP, paclitaxel, trastuzumab + pertuzumab; TKI, tyrosine kinase inhibitor; TROP2, trophoblast cell surface antigen 2; VEGF, vascular endothelial growth factor;

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