Katy Moore, Deputy Director at Stephenson Cancer Center, shared on X:
“Bender and colleagues in JCO, worth reading.
The argument
Some of the OS advantages that moved ADCs into first line in breast cancer may reflect where (globally) the trials enrolled rather than where the drug belongs in the sequence. Where crossover happened, OS tends not to separate.
We are positioned the same way in ovarian cancer. MIRASOL showed PFS and OS gains for mirvetuximab in platinum-resistant disease with no crossover permitted, and global availability is still limited.
So how will we interpret GLORIOSA which tested MIRV + bev vs bev maintenance in platinum sensitive recurrent disease? Primary endpoint is PFS. The sequencing question lives in the OS secondary and in what control-arm patients actually got at progression. Robust crossover with OS still separating would be definitive for moving MIRV up. Minimal crossover tells us the drug works but may not convince us that it works better earlier?
RAINFOL-01 and REJOICE-Ovarian 01 are evaluating topoisomerase 1 ADCs and will be first to result in the PROC setting. If positive (which I hope they are) they are years from global access. Meanwhile sac-TMT and T-DXd are in front-line maintenance now, PFS primary, OS secondary, small US footprint.
If those studies in front line are positive with no crossover, we will know an ADC works in front-line maintenance and still not know that front line is the best place to use it. Bender’s work suggests the need to a) fully report subsequent therapy, maybe beyond 1st subsequent therapy and b) report by region. Until we do, we cannot interpret our own OS data and best position these assets for our patients.”
Title: International Breast Cancer Trials and Optimal Sequence of Treatment
Authors: Uri Bender, Karine Ronan, Eitan Amir
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