Adjusting for treatment crossover in the MAVORIC trial: survival in advanced mycosis fungoides and Sezary syndrome

Background: Relative overall survival (OS) estimates reported in the MAVORIC trial are potentially confounded by a high proportion of patients randomized to vorinostat switching to mogamulizumab; furthermore, vorinostat is not used in clinical practice in the UK. Methods: Three methods were considered for crossover adjustment. Survival post-crossover adjustment was compared with data from the Hospital Episode Statistics (HES) to contextualize estimates. Results: Following adjustment, the OS hazard ratio for mogamulizumab versus vorinostat was 0.42 (95% CI: 0.18, 0.98) using the method considered most appropriate based on an assessment of assumptions and comparison with HES. Conclusions: OS of mogamulizumab relative to vorinostat may be underestimated in MAVORIC due to the presence of crossover. The HES database was used to validate this adjustment. Tweetable abstract The MAVORIC trial compares mogamulizumab with vorinostat in patients with mycosis fungoides and Sezary syndrome. Survival was confounded by 73% of vorinostat patients switching to mogamulizumab. After switching adjustment, the results suggested mogamulizumab improved overall survival.