Standing Platform Proposed for ctDNA-Guided Cancer Drug Development in Molecular Evidence of Disease
This Nature Reviews Cancer perspective proposes a standing trial infrastructure that continuously enrolls patients with molecular evidence of disease (ctDNA-positive after curative intent therapy) to accelerate adjuvant drug evaluation. Such trials could be smaller and faster than conventional adjuvant designs given the high recurrence probability and short time to relapse in MED-positive patients, with ctDNA serving as an early biomarker of treatment effect.
The original study
A standing platform for cancer drug development using ctDNA-based evidence of recurrence.
- Authors
- Medford AJ, Carmeli AB, Ritchie A, Wagle N, Garraway L, Lander ES, et al.
- Journal
- Nature reviews. Cancer
- Type
- Journal Article, Review
- PMID
- 39349822
Original abstract
The time required to conduct clinical trials limits the rate at which we can evaluate and deliver new treatment options to patients with cancer. New approaches to increase trial efficiency while maintaining rigor would benefit patients, especially in oncology, in which adjuvant trials hold promise for intercepting metastatic disease, but typically require large numbers of patients and many years to complete. We envision a standing platform - an infrastructure to support ongoing identification and trial enrolment of patients with cancer with early molecular evidence of disease (MED) after curative-intent therapy for early-stage cancer, based on the presence of circulating tumour DNA. MED strongly predicts subsequent recurrence, with the vast majority of patients showing radiographic evidence of disease within 18 months. Such a platform would allow efficient testing of many treatments, from small exploratory studies to larger pivotal trials. Trials enrolling patients with MED but without radiographic evidence of disease have the potential to advance drug evaluation because they can be smaller (given high probability of recurrence) and faster (given short time to recurrence) than conventional adjuvant trials. Circulating tumour DNA may also provide a valuable early biomarker of treatment effect, which would allow small signal-finding trials. In this Perspective, we discuss how such a platform could be established.