Time to progression ratio in cancer patients enrolled in early phase clinical trials: time for new guidelines?
Menée en France auprès d'une cohorte de 177 patients atteints d'un cancer de stade avancé et inclus dans des essais cliniques de phase 1/1b mettant en oeuvre plusieurs lignes de traitement, cette étude estime la valeur seuil du critère TTPr (time to progression ratio) permettant d'affirmer qu'un traitement est plus efficace qu'un autre en l'absence d'effet thérapeutique global
Background : Reliable evaluation of treatment benefit in early phase clinical trials is necessary. The time to progression ratio (TTPr), which compares successive TTP in a single patient, is a powerful criteria for determining targeted or immune therapies efficacy.
Methods : We evaluated 205 TTPr in a large cohort of 177 advanced cancer patients enrolled in at least two Phase 1/1b trials (out of 2827 phase 1/1b-treated patients) at Gustave Roussy.
Results : This first wide description of TTPr showed that, under the hypothesis of overall absence of treatment line effect, the median TTPr was 0.7 and that 25% of patients presented a TTPr above the conventional efficacy threshold of 1.3.
Conclusions : A higher median TTPr and a larger proportion of patients above the 1.3 threshold should therefore be achieved to conclude to drug efficacy. New guidelines for TTPr interpretation and calibration are proposed, which warrant independent prospective validation.
British Journal of Cancer , résumé, 2018