OnCo
ideasIdea

Randomised trials of stopping immunotherapy after one year versus continuing

Immunotherapy is often given for two years or until it stops working, but responses can last long after stopping. Trials that randomly assign responders to stop or continue would show whether the extra year is needed.

Non-inferiority trials randomising patients with response or stable disease after 12 months of PD-1/PD-L1 therapy to discontinuation with surveillance and retreatment at progression versus continuation to 24 months or beyond, with a 'treatment-free interval' and cumulative drug exposure as secondary endpoints. Several academic trials (e.g., in melanoma and NSCLC) are under way; the proposal is to make stop-versus-continue a standard post-approval requirement for durable-response agents.

Hypothesis
Stopping at 12 months in responders is non-inferior for OS with substantially lower cumulative toxicity and cost, and retreatment at progression recovers response in a meaningful fraction.
Rationale
Long-term follow-up of early checkpoint trials shows durable responses persisting for years after treatment ended; pharmacology suggests receptor occupancy persists for months.
What would test it
Pool the ongoing academic stop trials in a prospective meta-analysis with a pre-agreed non-inferiority margin; require sponsors of new checkpoint approvals to contribute to a duration trial.
Maturity
being tested at scale
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks
  • 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.
  • 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.
  • Toxicity and quality of life are undervalued · Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.

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