Table 1.

Relative merits of different endpoints in melanoma clinical trials

EndpointAdvantagesLimitations
Overall survivalGold standardQuality of life not necessarily considered
Will be difficult to achieve when control groups have high survival
High patient numbers then needed
Symptom relief not taken into account
Crossover designs make overall survival outcomes difficult to achieve
Long-term outcomes confounded by the clinical availability of other agents with similar mechanism of action
PFSOutcome more rapid and allows rapid selection of agentsNot necessarily related to overall survivalQuality of life not necessarily considered
If very prolonged may be an endpoint of merit in its own right
Response rateValuable in single-arm studies if “unprecedentedly” highNot necessarily a surrogate endpoint for overall survival benefit
Difficult to achieve when developing new agents with similar mechanism of action with already high response rates
Quality of lifeMay be a valid endpoint irrespective of effects of other endpointsNo information about benefits based on time-to-event endpoints

Abbreviation: PFS, progression-free survival.