The patients treated with Bisantrene were of worse prognosis...

The patients treated with Bisantrene were of worse prognosis than dox. You need to look at the adjusted HR.



I have recreated this table from an in vitro study investigating human tumor samples and comparing BIS, DOX, and MTX sensitivity. Clearly, Bisantrene is sensitive when the other anthracyclines are not.




This does not make sense when you consider Doxorubicin binds to DNA 155x stronger than Bisantrene.



It only makes sense when you consider the different biological targets of Bisantrene relative to Doxorubicin that drive cytotoxicity. What I find particularly interesting is the majority of these individual mechanistic targets have been shown to synergise with doxorubicin in multiple cancer types and mostly solid tumors. Like drugs of that era and inclusive of Doxorubicin, Bisantrene is pleiotropic by nature.



A complete review of the clinical history of Bisantrene demonstrates response rates improve with more regular dosing within the month. Thus, you also need to appreciate that the Q3W dosing regimen used in the P3 breast trial likely did not optimise Bisantrenes mechanistic targets.



In summary, Bisantrene non-significantly outperformed Doxorubicin (an FDA approved anthracycline and number 1 rated most essential drug in the world) in Overall Survival in this breast cancer population with a non-specific dosing regimen for its mechanistic targets. Therefore, the question you really want to be asking is what is the % likelihood chance that the combination of Bisantrene with Doxorubicin drives significantly better responses and overall survival with meaningful cardioprotection. Because Bisantrene has shown clear diffferential sensitivity in patients tumor samples and that each unique mechanism of action has shown synergy with the effects of Doxorubicin, I think the likelihood of this happening is very very high.

We really are not going to know until Bisantrene is used in a way that reflects its specific pleiotropic mechanistic nature.