ERIVEDGE was approved in 2012 to treat two forms of advanced skin cancer: locally advanced basal cell carcinoma (BCC), in which the cancer invades surrounding tissue, and metastatic BCC, in which the cancer spreads to other parts of the body. The original label specifies that patients take ERIVEDGE daily until either their disease progresses or side effects become intolerable.
Challenge we faced:
- In clinical practice, patients were experiencing muscle spasms which was causing them to discontinue treatment
- Given ERIVEDGE has a long half-life , the clin pharm team believed that dose interruption was possible.
- The team wondered if we could identify and guide clinicians on a duration for dosing break that gave the patients the relief needed, while maintaining efficacy.
What we did:
- The team developed a tumor dynamic model, predicted the relationship between dose-interruption and tumor size outcomes, enabled identification of this 8-week dosing interruption via virtual clinical trial simulations based on predictive modeling.
- Simulations show that, with a 8-week dose interruption, a) tumor size does not go up and b) the proportion of pts with ≥ 30% reduction in tumor size as a measure of efficacy was similar to continuous dosing.
- This modeling approach was validated using clinical data from multiple BCC study which investigated dosing interruptions
Outcome:
The team submitted this analysis in a sNDA filing to FDA to include, in the product label, the possibility to “withhold ERIVEDGE for up to 8 weeks for intolerable adverse reactions until improvement or resolution.”
FDA granted approval for up to 8-week dose interruption, without need for additional clinical study in BCC.
Why label optimization matters:
- Up to 31% patients experience treatment emergent adverse events leading to treatment discontinuation.
- Dosing tailored to the patients experience allows treatment interruptions thus enabling patients to stay on the medicine longer and receive more benefit
- Update of label using virtual clinical trial simulations
Towards precision dosing
A collaboration with the Moffitt cancer center will soon investigate in a small clinical study the benefit of personalized dosing for ERIVEDGE by individualizing the duration of the dose interruptions.
