# Immunotherapy before surgery rather than with chemoradiation (HNSCC)

Source: https://onco.cc/pairings/io-before-surgery-hnscc/  
OnCo record `io-before-surgery-hnscc` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In head and neck cancer, immunotherapy works when given before surgery but not when given alongside chemoradiation.

## Summary

This sequence rule in head and neck squamous cell carcinoma places immune checkpoint inhibitors before surgery rather than concurrently with modern external beam chemoradiation. T-cell priming needs an intact tumour and functioning lymphatics, and chemoradiation destroys both while the drug is on board; radiation-induced lymphopenia, steroids and loss of the antigen-rich primary are the proposed explanations. KEYNOTE-689, which gave pembrolizumab before and after surgery, improved event-free survival, whereas JAVELIN Head and Neck 100 and KEYNOTE-412, which gave it with chemoradiation, both failed. One positive phase 3 against two negative ones makes timing, not the drug, the lesson; the concept sits under neoadjuvant, adjuvant and perioperative therapy.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Immune checkpoint inhibitors + IMRT / IGRT (modern external beam)
- Type: sequence
- Rationale: T-cell priming needs an intact tumour and functioning lymphatics; chemoradiation destroys both while the drug is on board.
- Evidence: One positive phase 3 versus two negative ones with the alternative sequence.

## Sources

- ClinicalTrials.gov NCT03765918: KEYNOTE-689: https://clinicaltrials.gov/study/NCT03765918
- ClinicalTrials.gov NCT02952586: JAVELIN Head and Neck 100: https://clinicaltrials.gov/study/NCT02952586

## Connected records

- cancers: [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- terms: [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/)
- trials: [JAVELIN Head and Neck 100](https://onco.cc/trials/javelin-hn-100/), [KEYNOTE-689](https://onco.cc/trials/keynote-689/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/)

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