Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials

Area of Science:

• Oncology
• Clinical Trials
• Biostatistics

Background:

• Metastatic melanoma treatment has advanced with demonstrated overall survival benefits.
• Assessing progression-free survival (PFS) as a surrogate for overall survival (OS) is crucial for efficient clinical trial design.

Purpose of the Study:

• To evaluate the reliability of progression-free survival (PFS) as a surrogate for overall survival (OS) in metastatic melanoma.
• To perform a meta-analysis of randomized controlled trials (RCTs) to correlate PFS and OS outcomes.

Main Methods:

• Systematic review of RCTs comparing metastatic melanoma treatments against dacarbazine control.
• Meta-analysis correlating hazard ratios (HRs) for PFS and OS, using fixed and random-effects models.
• Sensitivity analyses conducted based on crossover rates, trial size, and dacarbazine dosage.

Main Results:

• 12 RCTs with 4416 patients were included, showing a strong correlation between PFS and OS treatment effects.
• Correlation coefficients ranged from 0.71 to 0.89 depending on the weighting strategy and statistical model.
• High crossover rates, particularly in later trials, weakened the PFS-OS correlation, but a robust correlation of 0.85 was observed in trials with minimal crossover.

Conclusions:

• Progression-free survival (PFS) is a robust surrogate for overall survival (OS) in dacarbazine-controlled metastatic melanoma trials.
• The strong correlation suggests PFS can reliably predict survival benefits in this patient population.
• This association is expected to remain valid as treatment standards evolve and influence future trial designs.