# Use a blood test at six weeks to decide whether to keep going

Source: https://onco.cc/ideas/idea-bio2-ctdna-six-week-io-switch/  
OnCo record `idea-bio2-ctdna-six-week-io-switch` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Scans at three months often cannot tell whether immunotherapy is working. A blood test at six weeks may give a clearer, earlier answer.

## Summary

On-treatment ctDNA change at four to eight weeks predicted checkpoint outcomes across tumour types in several cohorts, including pan-cancer analyses, and outperformed early imaging in distinguishing pseudoprogression from true progression. The step never taken is a randomised trial in which the ctDNA result actually drives the decision to continue, intensify or switch.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: A ctDNA-guided switch strategy at six weeks improves overall survival compared with imaging-guided management, by moving non-responders onto alternative therapy months earlier.
- Rationale: Molecular response precedes radiographic response, and the cost of continuing an ineffective checkpoint inhibitor is measured in months of lost opportunity as well as money. Interventional ctDNA guidance has already proved feasible in the adjuvant setting.
- Proposed test: A randomised strategy trial in advanced disease comparing ctDNA-guided with standard imaging-guided management, with overall survival as primary endpoint and drug cost as a pre-specified secondary.
- Maturity: early-clinical
- Actor: clinic

## Sources

- Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019): https://doi.org/10.1001/jamanetworkopen.2019.2535

## Connected records

- ideas: [CD8 PET to stop or switch immunotherapy early](https://onco.cc/ideas/idea-cd8-pet-io/), [Molecular-progression switching beyond ESR1](https://onco.cc/ideas/idea-ctdna-switch-generalised/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/), [RECIST](https://onco.cc/terms/recist/)
- bottlenecks: [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Prices and value](https://onco.cc/bottlenecks/b-drug-pricing/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- key papers: [Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs](https://onco.cc/key-papers/paper-haslam-jama-netw-open/)

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