Francesco Schettini: Which ADC is to prioritise in HR+ and TN BC?
Francesco Schettini, Medical Oncologist at the Breast Unit of the Hospital Clinic of Barcelona and Postdoc Researcher at the IDIBAPS, shared a post on X:
“Now that sacituzumab govitecan (SG) and trastu deruxtecan (TDXd) are available for CT-pretreated HER2-low MBC and ADC sequencing is scarcely effective, which ADC is to prioritise in HR+ and TN BC?
We tried to answer with our just-published network meta-analysis!”
“We retrieved data of efficacy and safety in HER2-low MBC for TDXd and SG from DB04, ASCENT and TROPiCS-02 to compare the 2 ADCs and ADCs vs CT in PFS, OS and side effects.
Then we added DB06 and TROPION-Breast01 for a secondary analysis including Dato-DXd and 1st line TDXd data.”
“SG and TDXd outperformed CT at the individual patient-level and at the trial-level both in HR+ and TN HER2-low MBC.
But, None of the 2 was clearly superior to the other in PFS/OS in both scenarios!
BUT TDXd had a higher likelihood of being superior to TDXd in HR+, and SG in HR+!”
“When adding the DB06 and TROPICS-Breast01 data (only HR+MBC), no ADC was superior to the others.
Still, TDXd was the ONLY ADC retaining a significantly superior benefit in terms of OS over standard CT!
This when including in the control arm more effective CT options (1st line).”
“Finally, as expected the safety profile between SG and TDXd differed significantly, leading also to different discontinuation rates.”
“So, while similar efficacy with T-DXd and SG in HER2-low MBC was observed, the evidence seem to support a bit more the use of SG in TN and TDXd in HR+HER2-low.
However, safety, drug availability, guidelines and patients’ preferences are ultimately key.
Dato-DXd role is uncertain!”
“I want to thank Guillermo Villacampa for the great statistical support and ideas, Aleix Prat, Kevin Punie, Matteo Lambertini, Rodrigo Sánchez-Bayona, Eva M Ciruelos, Sara Tolaney, Javier Cortes, Juanmi Cejalvo, Daniele Generali, Alessandra Gennari, Tomás Pascual and Maria Vidal and all co-authors 4 their invaluable contributions!”
“CORRECTION: TDXd had a higher likelihood of being superior to TDXd in HR+, and SG in TN!”
Efficacy and safety of antibody-drug conjugates in pretreated HER2-low metastatic breast cancer: A systematic review and network meta-analysis.
Authors: Francesco Schettini, et al.
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