How to report toxicity associated with targeted therapies?
Cet article présente deux méthodes pour mieux décrire l'évolution des effets indésirables associés aux thérapies ciblées dans les essais cliniques
Background In the era of personalized medicine, Molecularly Targeted Therapies (MTT) has modified the outcome of some cancer types. The price of tumour control needs to be balanced with toxicity since these new therapies are administered continuously for several months or sometimes for several years. For cytotoxic drugs, the incidence of adverse event (AE) was traditionally reported as frequency and intensity. This simple measure is not sufficient to capture the recurrent nature and duration of AE. This paper presents two methods to better describe the toxicity burden across the time: prevalence and Q-TWiST.
Patients and methods Limitation of worst grade method and advantages of prevalence and Q-TWiST in the analysis of toxicity were illustrated using data from a phase II trial and a hypothetical simulated clinical trial.
Results Prevalence integrates the recurrent nature of adverse event. Using prevalence, it's possible to obtain a time profile of AE. Q-TWiST method evaluates the weighted time spent in each health state and also considers the recurrent nature of side effects in order to assess the “risk-benefit” ratio of a treatment. When interpreting Q-TWiST results, it's necessary to take into account OS and PFS and to define a clinical relevant difference according to the setting
Conclusion The two methods presented here capture different effects. They are helpful for physicians in their treatment choice (balance benefit risk), to counsel patients and to optimize supportive care In order to ensure consistency and provide critical information required for medical decision-making, it is important to encourage the use of alternative statistical methods in the analysis of toxicities associated with MTT.
Annals of Oncology , résumé, 2016