ESMO Oncology Updates: What's New in Cancer Treatment This Week

January 05, 2026

ESMO Oncology Updates: What's New in Cancer Treatment This Week

The latest European Society for Medical Oncology (ESMO) research is reshaping how we treat cancer across multiple tumor types. Here's a breakdown of the most exciting advances—explained in practical terms for your clinic and patients.

Head and Neck Cancer: Adding More Immunotherapy = Better Outcomes

For years, we've relied on single checkpoint inhibitors for head and neck cancer. That's changing fast.

The Big News: Combo Immunotherapy Works

Multiple trials presented at ESMO 2025 show that combining immunotherapy drugs—either before or after surgery—gives better results than surgery alone.^[1]^[2]

The KEYNOTE-689 trial tested pembrolizumab given before and after surgery in patients with advanced, resectable head and neck cancer. Results? A 3-year event-free survival rate of 60% with combo therapy versus 46% with surgery alone. Even better: about 9% of patients had complete pathologic response (tumor nearly gone at surgery), compared to 0% in the surgery-only group.^[1]

What does this mean for you?

· Consider perioperative immunotherapy for patients with locally advanced disease

· Quality-of-life data shows faster recovery with this approach

· This is now becoming standard of care in many centers

The Emerging Trend: Why Stop at One Drug?

New research shows dual checkpoint inhibitors—combining different immune targets—may overcome resistance. Trials testing:

· Retifanlimab + LAG-3 and TIM-3 blocking: Higher response rates than single-agent PD-1 inhibitors

· Tiragolumab (TIGIT blocker) + atezolizumab: Early promise in recurrent/metastatic disease

· Enfortumab vedotin (a targeted drug) + pembrolizumab: Novel antibody-drug combination showing activity in first-line metastatic disease^[1]

Bottom line: Single-agent checkpoint inhibition is becoming outdated. Combinations are the future.

Gastric Cancer: The Claudin 18.2 Revolution

This is perhaps the most transformative area in upper GI oncology right now.

What is claudin 18.2?
It's a protein on the surface of gastric cancer cells that's almost never present in healthy stomach cells—making it a perfect target.

The MATTERHORN Trial: Durvalumab-FLOT Now Standard

Adding durvalumab (a PD-L1 inhibitor) to standard FLOT chemotherapy before surgery improved overall survival by 7% at 3 years (HR 0.78). The FDA has already approved this combination, making it the new treatment standard for resectable gastric and gastroesophageal cancer.^[3]

Key Point: This benefit worked regardless of PD-L1 tumor status—unusual for immunotherapy and important for patient selection.

The Game-Changer: New Claudin 18.2 Drugs

Presented at ESMO Asia Congress December 2025, JS107 (a claudin 18.2-targeting antibody) combined with immunotherapy and chemotherapy achieved an 87% response rate in patients with high claudin 18.2 expression. Patients are living longer, with median progression-free survival of 11 months.^[4]

ASP2138 (another claudin 18.2 drug) is moving into phase III trials. Early data suggest it works as monotherapy and in combinations. Phase III enrollment expected mid-2026.^[5]

What this means:

· Testing tumors for claudin 18.2 should become routine

· Patients with high expression will benefit from new targeted combinations

· This could replace traditional chemotherapy-only approaches

Esophageal Cancer: Immunotherapy is Standard, But Questions Remain

For metastatic esophageal squamous cell carcinoma with high PD-L1 expression, platinum chemotherapy + anti-PD-1 therapy is now standard first-line treatment.^[6]

The unmet need? We still don't have a clear optimal strategy after chemoradiotherapy fails. ESMO 2025 presentations explored this question, with new trial designs being refined for 2026 enrollment.

Liver Cancer: Triple Combinations Outperform Dual Therapy

For Advanced HCC

The gold standard has been atezolizumab + bevacizumab. Now, adding a third drug is showing promise.

The SKYSCRAPER-14 (IMbrave152) trial added tiragolumab (TIGIT inhibitor) to atezolizumab-bevacizumab, improving response rates from 11% to 43%. This isn't just about more responses—patients are staying on therapy longer with durable control.^[7]

ABC-HCC Trial: Immunotherapy Beats Locoregional Therapy?

Here's a stunning finding: In intermediate-stage HCC, atezolizumab-bevacizumab delayed disease progression longer than the traditional approach of TACE (a locoregional procedure). This challenges decades of practice standards and suggests systemic immunotherapy could replace TACE in selected patients.^[7]

For Bile Duct Cancer

The combination of toripalimab + lenvatinib + GEMOX chemotherapy achieved an 80% response rate in intrahepatic cholangiocarcinoma with median overall survival of 22.5 months. Some patients even became surgical candidates after this intensive therapy—rare in biliary cancers.^[7]

For advanced biliary tract cancer after chemotherapy fails, durvalumab + tremelimumab (dual checkpoint blockade) offers a late-line option, though with modest 10% response rates and 8-month median survival.^[7]

Bladder Cancer: Surgery is No Longer Enough

KEYNOTE-905: Antibody-Drug Combos Change the Game

For muscle-invasive bladder cancer, enfortumab vedotin + pembrolizumab given before surgery dramatically improved outcomes.^[8]

The Results:

· 57% of patients had complete pathologic response (cancer gone at surgery)

· Compare that to 9% with surgery alone—a 6-fold difference

· Event-free survival significantly improved

· Surgery was still safe and feasible

This represents a major shift toward giving targeted drug + immunotherapy upfront to "shrink" tumors before surgery.

POTOMAC: BCG Plus Immunotherapy for Early Disease

For high-risk non-muscle-invasive bladder cancer (early stages), adding durvalumab to BCG immunotherapy reduced recurrence risk by 32%. This is the first successful blend of checkpoint inhibition with BCG—the traditional treatment since the 1970s.^[8]

What This Means for Practice:

· Early MIBC: Consider perioperative immunotherapy

· NMIBC: BCG + durvalumab is now standard

· Precision approach: ctDNA-guided adjuvant therapy shows promise (IMvigor011 trial)—treat only those who need it

Kidney Cancer: Triple Therapy and Adjuvant Options Expand

First-Line Triple Combinations

The KEYMAKER-U03 trial tested belzutifan (HIF-2α inhibitor) + pembrolizumab + lenvatinib in untreated advanced kidney cancer. Results: 31.8-month median progression-free survival, outperforming dual therapy (20.8 months).^[8]

Translation: More intensive upfront therapy delays progression, but comes with more toxicity (70% grade 3+). Careful patient selection is needed.

Adjuvant (Post-Surgery) Therapy

The RAMPART trial showed that adjuvant durvalumab + tremelimumab (dual checkpoint blockade) after surgery improves disease-free survival in high-risk kidney cancer versus observation alone.^[8]

For Prostate Cancer

The EMBARK trial demonstrated that enzalutamide + leuprolide for high-risk, biochemically recurrent prostate cancer achieved 79% 8-year overall survival versus 70% with hormone therapy alone—a meaningful survival benefit maintained over nearly a decade.^[8]

The ICI Resistance Problem (And Solutions)

What happens when patients stop responding to checkpoint inhibitors? ESMO 2025 presented exciting new strategies.

GDF-15 Neutralization: Visugromab + Nivolumab

The GDFATHER-01 trial identified GDF-15—a "don't eat me" signal cancer cells produce—as a resistance mechanism to PD-1 inhibitors. Adding visugromab (anti-GDF-15) to nivolumab in ICI-refractory patients achieved:

· 61.5% complete/near-complete response rates

· Median response duration of 32+ months

· Responses deeper than patients' initial immunotherapy^[9]

What this means: We may be able to "rescue" patients who've already progressed on checkpoint inhibitors—a significant advance in a desperate situation.

mRNA Vaccine Approach: mRNA-4359 + Pembrolizumab

An mRNA vaccine encoding tumor antigens (PD-L1 and IDO1) combined with pembrolizumab showed 67% response rates in ICI-resistant melanoma. Remarkably safe with minimal toxicity despite prior heavy immunotherapy exposure.^[9]

VISTA Inhibitors: A Different Checkpoint

Solnerstotug (anti-VISTA) combined with cemiplimab in PD-L1-refractory patients achieved 14% response rate—proof that targeting different immune pathways can overcome resistance.^[9]

Bispecific Antibodies: Dual Pathway Blocking

INCA33890 simultaneously blocks PD-1 (immunosuppression) and TGFβR2 (tumor-suppressive microenvironment). This dual targeting addresses both immune cell exhaustion and immune exclusion—a sophisticated approach to truly "cold" tumors.^[10]

Skin Cancer: The Immunotherapy Era Arrives

Squamous Cell Carcinoma: Adjuvant Therapy Now Standard

The C-POST trial is practice-changing. For high-risk cutaneous squamous cell carcinoma (cSCC) after surgery, adjuvant cemiplimab significantly reduced recurrence and death:

The Numbers:

· 2-year disease-free survival: 87% with cemiplimab vs. 64% with placebo

· 68% reduction in recurrence/death risk

· Benefit consistent across all patient subgroups, even PD-L1-negative tumors

· Well-tolerated with no surprise toxicities^[11]

FDA Approval: October 2025—cemiplimab is now the first-line adjuvant standard for high-risk cSCC, replacing observation and older approaches.

For Your Practice:

· Risk stratify all cSCC patients using established criteria (size, depth, grade, margins, lymph node involvement)

· High-risk patients should receive 12 weeks of cemiplimab induction, then 6-week maintenance dosing

· Quality of life improved compared to observation

Basal Cell Carcinoma: Options Beyond Hedgehog Inhibitors

For advanced metastatic BCC, cemiplimab offers durable disease control in patients intolerant to or progressing on hedgehog pathway inhibitors (vismodegib, sonidegib).^[12]

Merkel Cell Carcinoma: First Adjuvant Immunotherapy Trial Shows Benefit

STAMP Trial: Pembrolizumab After Surgery

This is the first phase III trial of adjuvant immunotherapy in Merkel cell carcinoma (a rare, aggressive neuroendocrine skin cancer). Results:^[13]

· Pembrolizumab significantly reduced distant metastasis risk (HR 0.58; P=0.032)

· Particularly helpful for patients NOT receiving radiation therapy

· Safety acceptable (31% grade 3+ adverse events)

· Overall survival data pending

For Metastatic Merkel Cell Carcinoma:

Long-term data from JAVELIN Merkel 200 shows avelumab (first-line standard) achieves 4-year overall survival of 38%—remarkable improvement over chemotherapy's 10-14 months.^[14]

Bonus Finding: Thymic Health Predicts Immunotherapy Response

Research presented at ESMO 2025 discovered that thymic (immune organ) health correlates with better response to checkpoint inhibitors. This opens future possibilities for optimizing immunotherapy timing or potentially supporting thymic function in patients.^[15]

Key Takeaways for Your Practice

1. Perioperative Immunotherapy is Here

· Moving from salvage to curative-intent settings

· HNSCC, gastric cancer, and bladder cancer all benefit

· Works best with high-risk disease

2. Combination Immunotherapy > Single Agent

· Dual checkpoint blockade (PD-1 + LAG-3, TIGIT, TIM-3, VISTA)

· Combined with targeted drugs (ADCs, kinase inhibitors)

· Works for both first-line and resistant disease

3. Claudin 18.2 Testing is Essential

· New target in gastric cancer with excellent response rates

· Test all gastric/GEJ tumors

· Multiple drug options emerging

4. Adjuvant Immunotherapy is Standard for Skin Cancers

· High-risk cSCC: cemiplimab is now approved

· Merkel cell: adjuvant pembrolizumab showing benefit

5. Overcoming Resistance is Possible

· GDF-15 neutralization, mRNA vaccines, new checkpoints

· New bispecific antibodies targeting dual pathways

· Heavily pretreated patients aren't without options

6. Precision Biomarkers Matter More Than Ever

· PD-L1 status less predictive for some indications

· ctDNA-guided adjuvant therapy shows promise

· Tumor-specific targets (claudin 18.2) increasingly important

What's Next?

Phase III trials are underway for:

· ASP2138 (claudin 18.2) in gastric cancer

· Multiple VISTA and TGFβR2 combinations

· Expanded indications for ADCs across tumor types

The oncology landscape is evolving rapidly toward earlier, more intensive, biomarker-informed treatment—with better outcomes and manageable side effects.

Bottom line: 2025–2026 marks a transition from broad checkpoint inhibition to precision medicine with rational combinations designed for specific tumor vulnerabilities. Staying current with these advances is essential for delivering cutting-edge care.

Key References:

OncoDaily. "Top immunotherapy trials ESMO 2025 head and neck."^[1]

Cancer Therapy Advisor. "ESMO 2025 Head and Neck Cancer News."^[2]

Cromospharma. "ESMO 2025 Insights: What Will Really Change Oncology in 2026."^[3]

YouTube. "Upper GI cancer highlights from ESMO 2025."^[6]

ESMO Daily Reporter. "New Claudin 18.2 approach shows promise in gastric cancer."^[4]

PMC NIH. "CLDN18.2-Targeted Therapy in Gastrointestinal Cancers."^[5]

ESMO Daily Reporter. "Mixed outcomes with novel targeted therapies for HER2+ upper GI."^[16]

EMJ Reviews. "ESMO 2025 Abstract Highlights."^[17]

Digestive Cancers EU. "Progress in Liver and Bile Duct Cancer: New Insights from ESMO 2025."^[7]

Urology Times. "ESMO 2025 recap: Top trials in genitourinary oncology."^[8]

ESMO Daily Reporter. "Novel strategies show promise in overcoming resistance to immune checkpoint inhibitors."^[9]