Teaching pack: Oesophageal squamous cell carcinoma

Oesophageal squamous cell carcinoma arises from the squamous lining of the upper and middle oesophagus; tobacco, alcohol, scalding drinks, nutritional deficiency and achalasia are its causes, and TP53 and NOTCH1 mutations its genetics. Early lesions found by endoscopy, common in Japanese and Chinese screening programmes, are removed endoscopically. Locally advanced disease is treated either with neoadjuvant chemoradiation followed by surgery (CROSS) or with definitive chemoradiation alone, which cures a similar share in this histology; adjuvant nivolumab after chemoradiation and surgery lowers recurrence when residual disease remains (CheckMate 577). Advanced disease is treated with nivolumab plus chemotherapy or nivolumab plus ipilimumab (CheckMate 648) or pembrolizumab plus chemotherapy (KEYNOTE-590); Chinese trials with camrelizumab, tislelizumab, toripalimab and sintilimab have produced the same result.

• Immunotherapy added to chemotherapy improved survival in every first-line trial, including several run entirely in China.
• Organ preservation with definitive chemoradiation and surveillance is an accepted alternative to surgery in this histology.
• Endoscopic screening in China detects a large share of cancers at a curable stage.

1. 1992RTOG 85-01: chemoradiation beats radiotherapy alone
2. 2012CROSS: chemoradiation before surgery doubles survival
3. 2021CheckMate 577 and KEYNOTE-590 bring immunotherapy to oesophageal cancer
4. 2022CheckMate 648: nivolumab combinations first line

• Nivolumab (treatment)
• Tislelizumab (treatment)

• CheckMate 648 (phase 3, n=970): Overall survival, PD-L1 ≥1% (nivolumab + chemotherapy): 15.4 months vs 9.1 months, HR 0.54
• KEYNOTE-590 (phase 3, n=749): Overall survival, all patients: 12.4 months vs 9.8 months, HR 0.73
• CROSS (phase 3, n=366): Overall survival: 49.4 months vs 24 months, HR 0.68
• CheckMate 577 (phase 3, n=794): Disease-free survival: 22.4 months vs 11 months, HR 0.69
• A Study of Ifinatamab Deruxtecan in Subjects With Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) (IDeate-Esophageal01) (phase 3, n=510): result not yet recorded
• A Study to Compare the Efficacy and Safety of LY01015 and Opdivo® Combined Respectively With Chemotherapy in Advanced or Metastatic Esophageal Squamous Cell Carcinoma (phase 3, n=510): result not yet recorded

• Whether surgery can be omitted after a complete response to chemoradiation.
• Most cases worldwide present late without access to endoscopy.
• Nutrition, swallowing and quality of life during and after treatment.

1. What is the standard treatment for stage II-III triple-negative breast cancer today?
   Answer

   Neoadjuvant pembrolizumab with carboplatin/paclitaxel then anthracycline chemotherapy, surgery, and adjuvant pembrolizumab (KEYNOTE-522); adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA); capecitabine for residual disease without BRCA.
2. What fraction of advanced melanoma patients on nivolumab plus ipilimumab are alive at ten years?
   Answer

   About 43% overall survival (CheckMate 067), with melanoma-specific survival around 52%.
3. What were the first checkpoint inhibitor and the first ADC ever approved?
   Answer

   Ipilimumab (2011) was the first checkpoint inhibitor; gemtuzumab ozogamicin (Mylotarg, 2000) was the first ADC, withdrawn in 2010 and re-approved in 2017.
4. Which cooperative group ran the trial that put nivolumab into first-line Hodgkin lymphoma?
   Answer

   SWOG (S1826, nivolumab-AVD vs BV-AVD), leading to FDA approval in March 2026 for ages 12 and over.

• Wikipedia: https://en.wikipedia.org/wiki/Esophageal_cancer
• Wikipedia: https://en.wikipedia.org/wiki/Esophageal_cancer