Biotech Values

[DewDiligence]

Femara vs Tamoxifen study and the usefulness of mathematical models:

>…approximately 25% of patients in the tamoxifen arm selectively crossed over to Femara therapy. This cross-over took place after the tamoxifen arm was unblinded in 2005 and showed superiority of Femara monotherapy over tamoxifen monotherapy in improving disease-free survival and reducing the risk of recurrence. When correcting for this cross-over in the tamoxifen arm, a 19% reduction in risk of death (HR=0.81, 95% CI: 0.69-0.94) was observed in favour of Femara.<

This is a good example of the usefulness of mathematical models that correct for the mass crossovers which occur when a trial is unblinded due to showing a statsig benefit on the primary (non-survival) endpoint.

Three years ago, the disease-free survival (DFS) data from this head-to-head trial were reported and were a blowout win for Femara:

• 19% lower risk of local recurrence
• 27% lower risk of metastatic recurrence
• 21% lower risk of any recurrence (a blend of 19% and 27% figs above)
• 29% lower risk of recurrence in patents with lymph-node involvement at baseline
• 30% lower risk of recurrence in patients who received concurrent chemo

With DFS numbers like these from a large randomized trial, it would’ve been hard to believe that Femara does not in fact extend overall survival compared to Tamoxifen in the adjuvant breast-cancer setting. Thanks to the mathematical model above cited above, we can be confident that it does. HR=0.81 for overall survival sounds about right, intuitively.