Precision Dosing: More Is Not Always Better

Recent findings underscore the importance of precision in drug dosage, especially in oncology, where the maxim "more is not always better" truly applies.

👉 T-DXd approved at lower dose following dose optimization study

A recent dose optimization study of trastuzumab deruxtecan (T-DXd), a novel HER2-targeting antibody-drug conjugate, focused on two dosage levels, 5.4 mg/kg and 6.4 mg/kg, in treating HER2-mutant NSCLC.

The results were telling: the lower dose was approved based on its ability to maintain efficacy while reducing toxicity, particularly in interstitial lung disease.

👉 Sotorasib approved at higher dose following dose optimization study

In contrast, a dose optimization study of sotorasib, a KRAS G12C inhibitor, comparing 240mg to 960 mg resulted in approval at the higher dose for advanced NSCLC.

But let's dig into this a little deeper....

Patients given the 4x higher dose gained an overall survival of 1.3 months (13 months vs 11.7 at the lower dose).

PFS was 0.2 months SHORTER (5.4 months at 960mg vs 5.6 months at 240mg) compared to the lower dose.

I think I'd prefer to take the lower dose given this.

It would be great to see what is happening in the real-world for patients treated with sotorasib.

Physicians may still choose the lower dose for their patients, or back off to a lower dose after adverse events are observed.

For both sotorasib and T-DXd, the dose optimization data is highly informative for patient care.

🌟 Shout out for biomarkers!

Earlier in drug development, PK-PD analysis has a critical role in guiding safer, more effective dosing strategies in clinical trials, ensuring that patients receive the maximum benefit with the least risk. Don't neglect them!