Treatment-free Survival, a Novel Endpoint with Integrated Partitioned Survival Analysis, in the Setting of Cancer Therapy

Music City Center 

As a new twist on Q-TWiST methodology (Gelber et al, 1989), we proposed treatment-free survival as a novel outcome measure motivated by the development of immunotherapy-based treatments for advanced cancers. Overall survival is the gold-standard endpoint. Immunotherapy has prolonged survival in multiple advanced cancer settings, some in which durable cancer control without continual treatment has been possible; severe and persistent side effects are also possible. We aimed to elucidate how the prolonged overall survival time is spent, on and off treatment, with and without toxicity of the treatment. Treatment-free survival is defined as part of an integrated partitioned overall survival analysis, visualized by the area between Kaplan-Meier curves for two traditional time-to-event endpoints, time to first-line treatment cessation and time to second-line treatment initiation or death; and estimated by the difference in restricted mean survival times of the two endpoints. The integrated analysis introduces further partitioning of mean TFS and times on treatment into times with and without toxicity.

Endpoints

Oncology

Restricted mean survival time