ESMO Updates
Latest Oncology News and Research Updates from ESMO 2025
The European Society for Medical Oncology (ESMO) Congress 2025, held in Berlin from October 17-21, marked the Society's 50th anniversary and brought together over 37,000 oncology professionals. The Congress delivered numerous practice-changing results across multiple tumor types, with several key updates in the areas you specified.oncodaily
Head and Neck Cancer
KEYNOTE-689: A New Standard in Resectable Disease
The phase III KEYNOTE-689 trial established perioperative pembrolizumab as a breakthrough treatment for resectable locally advanced head and neck squamous cell carcinoma (HNSCC). The study demonstrated that adding neoadjuvant and adjuvant pembrolizumab to standard-of-care surgery followed by radiotherapy (with or without cisplatin) significantly improved event-free survival compared to standard care alone.ecancer+1
Key findings include a median event-free survival of 51.8 months with pembrolizumab versus 30.4 months with standard of care. The three-year data showed a 10% reduction in risk of distant metastases, and notably, the treatment worked particularly well in patients with high PD-L1 expression but demonstrated benefits across all tumor types. Based on these results, the FDA approved pembrolizumab in June 2025 for adults with resectable locally advanced HNSCC.ascopost+2
CAMORAL and Other Immunotherapy Combinations
The CAMORAL study evaluated camrelizumab (a PD-1 inhibitor) combined with chemotherapy as perioperative treatment for locally advanced HNSCC, assessing pathological response and disease-free survival outcomes. Additionally, preliminary data from enfortumab vedotin plus pembrolizumab in recurrent HNSCC showed a 39% response rate with a complete response rate of 9.8%.oncodaily+1
The Skyscraper-09 study evaluating tiragolumab plus atezolizumab in first-line PD-L1≥5% head and neck cancer demonstrated numerical improvements in response rates (21.3% vs 15.4%) and median overall survival (16.2 months vs 13.6 months), with particularly promising results in patients with PD-L1≥20% expression.oncologypipeline
Upper Gastrointestinal Cancer
MATTERHORN: Durvalumab Establishes New Standard in Gastric Cancer
The MATTERHORN trial presented final overall survival data demonstrating that adding durvalumab to perioperative FLOT chemotherapy (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) significantly improves outcomes in resectable gastric and gastroesophageal junction adenocarcinoma.ascopost+1
| Outcome | Durvalumab + FLOT | Placebo + FLOT |
|---|---|---|
| 36-month Overall Survival | 68.6%ascopost | 61.9%ascopost |
| Hazard Ratio for OS | 0.78 (p=0.021)ascopost | — |
| Median Event-free Survival | Not reachedoncodaily | 32.8 monthsoncodaily |
HER2-Positive Upper GI Cancers: Mixed Results
The KC-WISE trial demonstrated that anbenitamab, a novel HER2-targeted bispecific antibody, combined with chemotherapy achieved remarkable outcomes in previously treated HER2-positive gastric cancer:dailyreporter.esmo+1
75% reduction in risk of progression or death
71% reduction in risk of death
Median overall survival of 19.6 months vs 11.5 months with chemotherapy alone
Overall response rate of 55.8% vs 10.8%
However, caution was noted regarding the study's limited geographic restriction to Chinese centers, necessitating international validation.dailyreporter.esmo
LEAP-014: Negative Results in Esophageal Cancer
The phase III LEAP-014 study found that adding lenvatinib to pembrolizumab plus chemotherapy did not improve overall survival in first-line metastatic esophageal squamous cell carcinoma (17.6 months vs 15.5 months), leading to study termination for futility.ascopost+1
Hepatobiliary Cancer
Hepatocellular Carcinoma: Advancing Treatment Paradigms
Atezolizumab plus bevacizumab versus TACE: The ABC-HCC trial and TALENTACE trial provided important data on systemic immunotherapy for intermediate-stage HCC. The TALENTACE trial showed that atezolizumab plus bevacizumab after TACE significantly improved progression-free survival (11.3 months vs 7.0 months; HR 0.71) compared to TACE alone, with higher response rates (49.1% vs 33.9%).digestivecancers+1
TIGIT disappointment: The phase III IMbrave152/SKYSCRAPER-14 trial evaluating the addition of tiragolumab to atezolizumab plus bevacizumab in first-line HCC failed to meet its primary endpoint of progression-free survival (8.3 months vs 8.2 months), continuing Roche's series of TIGIT setbacks.clinicaltrialsarena+1
Biliary Tract Cancer
The IMMUNOBIL trial evaluated dual immunotherapy with durvalumab and tremelimumab for advanced biliary tract cancer after chemotherapy progression. Results showed the combination was well-tolerated but offered modest benefits: approximately 10% response rate and median overall survival of about 8 months.digestivecancers
A promising development came from the toripalimab, lenvatinib, and GEMOX combination as neoadjuvant treatment for intrahepatic cholangiocarcinoma, achieving 80% tumor shrinkage and enabling several previously inoperable patients to become surgical candidates, with median overall survival of 22.5 months.digestivecancers
Genitourinary Cancers
Bladder Cancer: Multiple Practice-Changing Trials
KEYNOTE-905/EV-303: This landmark trial demonstrated that perioperative enfortumab vedotin plus pembrolizumab dramatically improves outcomes in cisplatin-ineligible muscle-invasive bladder cancer:urologytimes+2
60% reduction in risk of recurrence, progression, or death
50% reduction in risk of death
Pathological complete response rate of 57.1% vs 8.6%
These results position EV plus pembrolizumab as a new standard of care for cisplatin-ineligible patients.dailyreporter.esmo
IMvigor011: This groundbreaking trial demonstrated that ctDNA-guided adjuvant therapy significantly improves outcomes in muscle-invasive bladder cancer:ecancer+2
ctDNA-positive patients receiving atezolizumab had a 36% lower risk of disease recurrence
41% reduction in risk of death
ctDNA-negative patients showed excellent outcomes without adjuvant therapy (2-year DFS = 88.4%)
This represents the first level 1 evidence supporting molecular residual disease-guided treatment in bladder cancer.dailyreporter.esmo
POTOMAC: Final analysis confirmed that durvalumab plus BCG induction and maintenance significantly improves disease-free survival (HR 0.68) in BCG-naive, high-risk non-muscle-invasive bladder cancer compared to BCG alone, with over 5 years of follow-up.ascopost+1
Prostate Cancer: EMBARK Confirms Survival Benefit
The EMBARK trial reported final overall survival data showing that enzalutamide plus leuprolide significantly improves outcomes in high-risk, biochemically recurrent prostate cancer:grandroundsinurology+2
8-year OS rate: 78.9% vs 69.5% with leuprolide alone
41% reduction in hazard of death
Consistent benefits across all subgroups
Enzalutamide monotherapy did not reach statistical significance for OS
This establishes enzalutamide plus ADT as standard of care for high-risk biochemical recurrence.oncologynewscentral
Kidney Cancer
The KEYMAKER-U03 substudy 3A evaluated triplet combinations including belzutifan plus pembrolizumab plus lenvatinib for first-line advanced clear cell renal cell carcinoma, showing promising response rates of 77.5% and progression-free survival exceeding 30 months.kidneycancer
The LenCabo trial comparing lenvatinib plus everolimus versus cabozantinib in metastatic clear cell RCC after PD-1 therapy demonstrated significantly longer median PFS with lenvatinib plus everolimus (15.7 months vs 10.2 months; HR 0.51), potentially informing optimal treatment sequencing.openhealthgroup+1
Immunotherapy Updates
Novel Strategies to Overcome Checkpoint Inhibitor Resistance
Several innovative approaches showed promise in heavily pre-treated, ICI-resistant patients:dailyreporter.esmo
GDF-15 blockade: The GDFATHER-01 trial evaluating visugromab plus nivolumab in ICI-resistant cancers demonstrated:
Complete or complete metabolic responses in 61.5% of responders
Median duration of response: 32.2 months (NSCLC), 28.8 months (UC), 19.4 months (HCC)
mRNA-based therapy: The mRNA-4359 vaccine encoding PD-L1 and IDO1 antigens combined with pembrolizumab achieved a 24% response rate in checkpoint inhibitor-resistant melanoma, with all responders having PD-L1 TPS ≥1%.dailyreporter.esmo
VISTA targeting: Solnerstotug combined with cemiplimab showed 14% ORR in advanced solid tumors resistant to prior anti-PD-(L)1 therapy.dailyreporter.esmo
CMV Serostatus as Biomarker
Research from the Fairfax lab presented at ESMO 2025 demonstrated that CMV seropositivity correlates with improved treatment outcomes in melanoma patients receiving single-agent anti-PD-1 immunotherapy, positioning CMV serostatus as a potential peripheral biomarker for predicting ICI response.oncology.ox
Non-Melanoma Skin Cancer
Merkel Cell Carcinoma: STAMP Trial
The phase III STAMP trial evaluated adjuvant pembrolizumab for Merkel cell carcinoma following surgical resection:ecancer+2
2-year recurrence-free survival: 73% vs 66% with observation (not statistically significant)
42% lower risk of developing distant metastases
Represents the largest clinical study to date in adjuvant MCC
The findings provide first evidence that adjuvant immunotherapy may help prevent distant spread in this aggressive, rare skin cancer.ecancer
Cutaneous Squamous Cell Carcinoma
Based on data from the C-POST trial, the FDA approved cemiplimab in October 2025 for adjuvant treatment of cutaneous squamous cell carcinoma at high risk of recurrence after surgery.esmo+1
Basal Cell Carcinoma
Real-world data on Hedgehog pathway inhibitors (vismodegib and sonidegib) presented at ESMO showed:
Sonidegib: 89.5% ORR, 36.8% complete response
Vismodegib: 65% ORR, 27.5% complete response
Patients switched from vismodegib to sonidegib maintained effectiveness (71.4% ORR)pubmed.ncbi.nlm.nih
For patients who progress on Hedgehog inhibitors, cemiplimab remains an approved option for locally advanced or metastatic BCC.esmo
Key Takeaways and Clinical Implications
The ESMO 2025 Congress delivered several paradigm-shifting findings that will reshape clinical practice:
Practice-changing positive results include perioperative pembrolizumab in head and neck cancer (KEYNOTE-689), durvalumab plus FLOT in gastric cancer (MATTERHORN), enfortumab vedotin plus pembrolizumab in bladder cancer (KEYNOTE-905), ctDNA-guided therapy in bladder cancer (IMvigor011), and enzalutamide plus ADT in prostate cancer (EMBARK).
Important negative results that equally inform practice include the TIGIT triplet failure in HCC (SKYSCRAPER-14), lenvatinib addition in esophageal cancer (LEAP-014), and the lack of enzalutamide monotherapy benefit for OS in prostate cancer.
The Congress also highlighted the growing role of biomarker-guided therapy, particularly ctDNA for treatment selection, antibody-drug conjugates expanding into earlier disease settings, and novel immunotherapy combinations to overcome checkpoint inhibitor resistance.apices+2
