Immunotherapies
Median survival
Mean survival
Weibull
Median Survival or Mean Survival: Which Measure Is the Most Appropriate for Patients, Physicians, and Policymakers?
Summary
- The average Restricted Mean Survival Time (RMST) for modern oncology agents approved by the FDA from 2013 to 2017 is 3.6 months, which is lower than the average median Overall Survival (OS) or Progression-Free Survival (PFS) of 4.6 months. When assuming a Weibull distribution post-trial, the average mean OS or PFS increases to 6.1 months.
- Immuno-oncology agents show significant improvements in mean versus median survival, with an average mean survival of 6.9 months using the Weibull distribution, compared to an average median of 3.2 months. Median survival alone is insufficient to understand efficacy in these cases.
- Biomarker-driven targeted therapies performed better across all survival measures, with median survival at 5.9 months, RMST at 4.6 months, and mean survival at 7.4 months.
- VEGF-targeted therapies have poorer outcomes with median survival of 2.1 months, RMST of 2.0 months, and mean survival of 2.2 months.
- The discrepancy between mean and median survival is most pronounced in immuno-oncology agents due to potential durable survival in a minority of patients. Mean survival captures long-term outcomes better than median survival.
- Using mean survival as a complementary measure in reporting prospective trials can provide valuable insights, particularly for immuno-oncology agents, and help clinicians and payers understand long-term impacts and make informed decisions.
- Recent value-based frameworks emphasize the need to understand the true benefit of innovative treatments, focusing on the tail of survival curves and potential durable survival in some patients.
- The study highlights limitations, including the interpretation of RMST depending on trial cut-off times, uncertainty in survival extrapolation using Weibull distribution, and potential contamination of mean survival measures due to censoring.
- Incorporating RMST alongside median survival in clinical trial reporting can offer more meaningful information for various stakeholders, although mean measures may be less significant for immuno-oncology agents compared to milestone reporting.
Understanding the efficacy of treatments is crucial for patients, physicians, and policymakers. Median survival, the most common measure used in the outcome reporting of oncology clinical trials, is easy to understand; however, it describes only a single time point. The interpretation of the hazard ratio is difficult, and its underlying statistical assumptions are not always met. The objective of this study was to evaluate alternative measures based on the mean benefit of novel oncology treatments.
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Immunotherapies, Median survival, Mean survival, Weibull
