Sorry if not clear. Pfs is surrogate endpoint because in settings where it is believed that death is a direct consequence of tumor progression. In the age where there was limited options, even a weak pfs can translate into an Os benefit.
As the number of treatment options increases the Pfs- OS correlation relationship breaks down, especially in front line therapy where os is so long that between pd and death additional anti ca rx can be given, assessment of Pfs still is a treatment comparison, however the OS analysis becomes comparison of the sequences of treatment plus subsequent treatments. All I am saying is that in this subset of patients who has almost exhausted treatment options after 5to 6 chemos already.
Well regarding imbalance there are lots more prognostic factors than just prior nmber of treatment.
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