Paolo Tarantino, Clinical Research Fellow at Dana-Farber Cancer Institute, shared a post on X:
A few thoughts on crossover in the Trop2 ADC trials.
- Crossover is ethical and critical in sequence clinical trials, ie. when a drug is approved in later lines and the trial tests an earlier use. ASCENT-03 falls into this category, since SG was approved for pretreated mTNBC when the trial started. Kudos to investigators and sponsor.
- TROPION-Breast02 was correctly designed without crossover. Indeed, when the trial started, Dato-DXd was still an investigational drug, with unclear benefit for pts with mTNBC. In line with this design, Dato-DXd had to reach a higher bar, with dual primary endpoints of PFS and OS
- Despite the different design, both trials eventually had many pts that received a subsequent ADC. In ASCENT-03, ~50% of pts in the control arm that received further Tx got SG, while in TB-02, ~30% of pts in the control arm that received further Tx got an ADC (mostly SG).
- While crossover makes OS challenging to compare, it does not affect PFS, ORR and toxicities. These should also not be directly compared, given slightly different trial population/designs, yet will eventually be the factors that help physicians chose one ADC over the other.
- What this story teaches us is that ADC trials are becoming increasingly difficult to interpret and compare, given widespread ADC use. Also, that understanding crossover is key to understanding the results of clinical trials
A good read on the topic here:
Title: Problematic crossovers in cancer drug trials
Authors: Bishal Gyawali
Read the Full Article.
Datopotamab Deruxtecan Improves PFS and OS in First-Line Advanced TNBC in TROPION-Breast02
