The importance of jointly analyzing treatment administration and toxicity associated with targeted therapies: a case study of regorafenib in soft tissue sarcoma patients

Abstract

Background

Different methods have been proposed to analyze adverse events (AEs) associated with targeted therapies. While these AEs lead to dose adjustments for many patients, conventional reporting methods do not take drug administration into consideration. This paper underlines the importance of jointly reporting AEs and drug administration using prevalence, and proposes a complementary approach to reporting.

Patients and methods

The prevalence method estimates the probability of progression-free patients being in a particular health state (State 1: AEs with full dose, State 2: AEs with reduced dose, State 3: no AEs with reduced dose) at different time points. To take into account the impact of dose adjustments on efficacy, the weighted prevalence method can be used by assigning utility weights to the different health states. The benefit of these methods was illustrated using data from a phase II trial of regorafenib.

Results

Only 4.6% of progression-free patients developed mucositis/stomatitis (grade≥2) at three months. The prevalence of patients not experiencing this AE but whose dose was reduced or treatment interrupted was 58.1%. The weighted prevalence of the regorafenib toxicity profile and dose reduction was higher in the control arm.

Conclusion

This case study confirms the importance of jointly analyzing AEs and drug administration. The weighted prevalence approach is an average score which incorporates the dimension of drug administration into AE assessment. This can be helpful for regulatory agencies as well as for clinicians to evaluate the benefit-risk ratio of therapies in their treatment choice.

Clinical trial

NCT01900743