# Reduce the dose once the cancer responds: response-adapted de-escalation trials

Source: https://onco.cc/ideas/idea-tr1-response-adapted-dose-reduction/  
OnCo record `idea-tr1-response-adapted-dose-reduction` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The dose needed to shrink a tumour may be higher than the dose needed to keep it from growing back. Trials that lower the dose once a response is achieved could reduce long-term side effects without losing control.

## Summary

Randomised trials in which patients achieving a defined response (radiographic, molecular or biochemical) after induction are allocated to continue full dose or step down to a maintenance dose (e.g., 50 percent), with resumption of full dose on progression. Precedents include dose reduction of dasatinib and other TKIs in chronic-phase CML after deep response, and maintenance de-escalation strategies in myeloma; the proposal extends the approach to solid-tumour targeted agents and ADCs where chronic toxicity accumulates.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Response-adapted de-escalation will be non-inferior for PFS with a substantial reduction in cumulative toxicity and cost, and progression on the reduced dose will be salvageable by re-escalation in most cases.
- Rationale: Tumour burden and the number of cells that must be suppressed fall after response; pharmacological suppression of residual disease may require less exposure than debulking, as CML dose-reduction studies suggest.
- Proposed test: Randomised phase 3 non-inferiority trials in two settings (an oral targeted agent in a solid tumour and an ADC) with PFS primary and cumulative toxicity, QoL and cost as secondaries.
- Maturity: early-clinical
- Actor: research

## Sources

- Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus

## Connected records

- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Imatinib](https://onco.cc/drugs/imatinib/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- roadmaps: [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/), [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/)

---
JSON: https://onco.cc/api/v1/entities/idea-tr1-response-adapted-dose-reduction.json