Trials for oesophagus carcinoma
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"esophageal carcinoma" AND "clinical trial"
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oesophageal carcinoma clinical trials 2025 2026 immunotherapy targeted therapy results
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"esophageal cancer" AND (nivolumab OR pembrolizumab OR immunotherapy)
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PMID: 41595220
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"esophageal cancer" AND (neoadjuvant OR perioperative OR adjuvant) AND (chemotherapy OR chemoradiotherapy)
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PMID: 41259897
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PMID: 36322089
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PMID: 39842010
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PMID: 38956195
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PMID: 40779895
Here is a comprehensive, evidence-based summary of clinical trials for oesophageal carcinoma, organized by treatment setting:
Clinical Trials in Oesophageal Carcinoma
1. Resectable / Locally Advanced Disease
A. Neoadjuvant Chemoradiotherapy - The CROSS Trial (Landmark)
The CROSS trial established neoadjuvant carboplatin + paclitaxel with concurrent radiotherapy (41.4 Gy) followed by surgery as a standard of care for resectable oesophageal cancer. It showed significantly improved R0 resection rates and overall survival vs. surgery alone, particularly in adenocarcinoma and squamous cell carcinoma (SCC).
B. ESOPEC Trial - FLOT vs. Chemoradiotherapy (NEJM 2025)
The most significant recent shift came from the ESOPEC trial (PMID 39842010), a phase III RCT published in the New England Journal of Medicine (January 2025):
- Design: Perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) + surgery vs. preoperative chemoradiotherapy (CROSS regimen) + surgery in resectable oesophageal adenocarcinoma (n=438)
- Results (median follow-up 55 months):
- 3-year OS: 57.4% (FLOT) vs. 50.7% (chemoRT) - HR 0.70, 95% CI 0.53-0.92, p=0.01
- 3-year PFS: 51.6% vs. 35.0% (HR 0.66)
- Conclusion: Perioperative FLOT is now the preferred standard over preoperative chemoradiotherapy for resectable oesophageal adenocarcinoma.
C. MATTERHORN Trial - Durvalumab + FLOT (Perioperative)
Adding the PD-L1 inhibitor durvalumab to perioperative FLOT improved event-free survival in resectable gastro-oesophageal adenocarcinoma. A 2025 meta-analysis (PMID 40779895) of phase III trials concluded that FLOT + checkpoint inhibitor (IO) should now be considered the preferred standard in resectable locally advanced gastro-oesophageal adenocarcinoma, pending mature OS data.
D. ESCORT-NEO/NCCES01 - Camrelizumab + Chemotherapy (Nature Medicine 2024)
Phase III RCT (PMID 38956195) in resectable thoracic oesophageal SCC:
- 391 patients randomized to: camrelizumab (PD-1 inhibitor) + nab-paclitaxel/cisplatin, camrelizumab + paclitaxel/cisplatin, or paclitaxel/cisplatin alone
- pCR rates: 28.0% (Cam+nab-TP) vs. 15.4% (Cam+TP) vs. 4.7% (TP alone) - both immunotherapy arms significantly superior (p<0.0001)
- Event-free survival data still maturing
E. Neoadjuvant IO + ChemoRT Meta-analysis (JAMA Netw Open 2022)
A meta-analysis of 27 trials (815 patients) (PMID 36322089) found pooled pathological complete response (pCR) rates with neoadjuvant IO + chemotherapy of:
- Overall pCR: 31.4% (95% CI 27.6-35.3%)
- pCR in SCC: 32.4%; in adenocarcinoma: 25.2%
- R0 resection rate: 98.6%; grade ≥3 adverse events: 26.9%
F. Perioperative IO + Chemotherapy (2025 Bibliometric Meta-analysis)
Wang et al. 2025 (PMID 41346615) confirmed neoadjuvant IO-based therapy improves pCR and MPR rates, with PD-1 inhibitor combinations showing superior outcomes vs. PD-L1 inhibitors in oesophageal SCC.
G. Neoadjuvant ChemoRT vs. Chemotherapy Alone in SCC (Ann Oncol 2023)
Tang et al. (PMID 36400384) - multicenter RCT in locally advanced oesophageal SCC comparing neoadjuvant chemoRT vs. chemotherapy alone before minimally invasive esophagectomy. Chemoradiotherapy achieved higher pCR but both had comparable survival outcomes.
H. S-1 Chemoradiotherapy in Elderly (Phase III, 2026)
Phase III multicenter RCT (PMID 41412437) - S-1-based chemoradiotherapy in inoperable elderly patients with oesophageal carcinoma showed long-term benefit with manageable toxicity.
2. Advanced / Metastatic Disease - First-Line
A. KEYNOTE-590 - Pembrolizumab + Chemotherapy (5-Year Data, ESMO Open 2025)
The definitive immunotherapy trial in advanced oesophageal cancer (PMID 41259897):
- Design: Pembrolizumab + cisplatin/5-FU vs. placebo + chemotherapy in previously untreated advanced oesophageal cancer or Siewert type 1 GEJ cancer (n=749)
- 5-year results (median follow-up 58.8 months):
- Median OS: 12.3 vs. 9.8 months (HR 0.72, 95% CI 0.62-0.84)
- 5-year OS: 10.6% vs. 3.0% (>3-fold improvement)
- 5-year PFS: 5.5% vs. not reached
- Conclusion: Pembrolizumab + chemotherapy is the standard first-line treatment for advanced oesophageal cancer with PD-L1 CPS ≥1. The 5-year data confirm durable benefit.
B. CheckMate 649 / Nivolumab
Nivolumab + chemotherapy (or nivolumab + ipilimumab) is approved in first-line gastro-oesophageal adenocarcinoma based on CheckMate 649 data, showing OS benefit with nivolumab + chemotherapy vs. chemotherapy alone.
C. Toripalimab Meta-analysis (J Gastrointest Cancer 2025)
A 2025 systematic review and meta-analysis (PMID 40624169) confirmed toripalimab (Chinese PD-1 inhibitor) improves outcomes in oesophageal cancer both in the neoadjuvant and advanced settings.
D. Perioperative Toripalimab + Chemotherapy (Phase III Interim, Cancer Commun 2024)
RCT interim analysis (PMID 39221992) - perioperative toripalimab + neoadjuvant chemotherapy showed improved outcomes in resectable oesophageal cancer.
3. ASCO 2026 Guidelines Update
The ASCO Guideline on Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer was updated in February 2026 (Shah MA et al., J Clin Oncol 2026), incorporating the latest trial data. Key updates include:
- Mandatory DPYD genetic testing before fluoropyrimidine-based chemotherapy
- Refined PD-L1 CPS thresholds for IO selection
- HER2 testing for all patients with adenocarcinoma
4. Emerging / Early-Phase Trials
| Trial/Agent | Type | Stage | Status |
|---|---|---|---|
| CAR T-cell therapy (Phase I) | Adoptive cell transfer | Metastatic/recurrent | Phase I, FDA-approved IND, preliminary results expected 2026 |
| BTLA inhibitor tiriifcemalimab + toripalimab (BT-NICE) | Neoadjuvant IO combo | Resectable ESCC | Phase I/II exploratory |
| Nivolumab + ipilimumab + CROSS | Neoadjuvant IO + chemoRT + surgery | Locally advanced adenocarcinoma/GEJ | Phase II/III ongoing |
| Nivolumab + paclitaxel + ramucirumab (2nd line) | IO + antiangiogenic | Advanced gastro-oesophageal | Phase II/III active |
5. Summary of Treatment Algorithm by Setting
| Setting | Histology | Current Standard (2026) |
|---|---|---|
| Resectable locally advanced | Adenocarcinoma | Perioperative FLOT ± durvalumab (ESOPEC + MATTERHORN) |
| Resectable locally advanced | SCC | Neoadjuvant chemoRT (CROSS) or neoadjuvant IO + chemo (ESCORT-NEO) |
| Advanced/metastatic 1st line | Both | Pembrolizumab or nivolumab + platinum/fluoropyrimidine (CPS ≥1) |
| Advanced HER2+ adenocarcinoma | Adenocarcinoma | Nivolumab + trastuzumab + chemotherapy (ToGA/CheckMate 811 data) |
| Inoperable elderly | Any | S-1-based chemoradiotherapy (Phase III, 2026) |
Key takeaways for 2026:
- Perioperative FLOT now surpasses the CROSS regimen in resectable adenocarcinoma (ESOPEC, NEJM 2025)
- Adding a checkpoint inhibitor (durvalumab or pembrolizumab) to FLOT is increasingly considered the new standard (MATTERHORN trial), pending mature OS data
- 5-year KEYNOTE-590 data confirm durable pembrolizumab benefit in advanced disease (5-year OS tripled: 10.6% vs. 3.0%)
- PD-1 inhibitors (camrelizumab, toripalimab, sintilimab) are showing strong phase III pCR data in neoadjuvant SCC setting in Chinese populations
- CAR-T cell therapy is entering Phase I in metastatic oesophageal cancer
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