OnCo
ideasIdea

Switch drugs at maximum response, not at relapse

Species go extinct when a second disaster hits a population already shrunk by a first one. Apply the same logic: hit the tumour with a different kind of drug when it is smallest, rather than waiting for it to grow back.

The first-strike, second-strike model from extinction biology proposes that a therapy switch at nadir, when the residual population is small and less diverse, exploits stochastic extinction and pre-empts the expansion of resistant clones. Current practice continues the first drug until progression, when the population is large and resistant. A trial would randomise patients at best response to a mechanistically distinct second strike versus continuation.

Hypothesis
In patients achieving deep response on a targeted agent, a time-limited switch to a non-cross-resistant agent at nadir increases the rate of durable remission at three years compared with continuing the first agent to progression.
Rationale
Small populations are more vulnerable to extinction; the mechanism is well established in ecology and is implicit in consolidation strategies in leukaemia, but has never been tested in solid tumours.
What would test it
Phase 2 in ALK-positive lung cancer or BRAF melanoma: at confirmed best response, randomise to three months of a different mechanism (for example chemotherapy or an ADC) followed by original therapy, versus continuation; endpoint durable remission at 36 months.
Maturity
speculative
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
5
Bottlenecks it attacks

Connected

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