ideasIdea
Use a blood test at six weeks to decide whether to keep going
Scans at three months often cannot tell whether immunotherapy is working. A blood test at six weeks may give a clearer, earlier answer.
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.
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.
What would test it
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
Who has to act
clinic
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.
- Prices and value · New cancer drugs routinely cost over $150,000 a year, often for months of benefit. Systems cannot afford them and patients go bankrupt.
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.