Overall survival |
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Long time to assess the results Confounded by subsequent therapy Confounded by other causes of death unrelated to cancer Higher cost of the trial
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Quality of life (QoL) |
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Less established as primary endpoint in early-phase therapeutic studies May encounter challenge in selection of relevant questionnaires. Disease-specific measurements may be less comprehensive Lengthy questionnaires can be time-consuming for the patients to complete Many studies lack per protocol minimally important difference and plan for missing data handling
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Disease-free survival or progression-free survival |
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Absence of progressive disease does not necessarily mean clinical benefit if toxicity is high and there is no impact on overall survival Time-dependent biases (lead-time bias, informative censoring) Late toxicities (secondary malignancies, other) are not captured No clear correlation with overall survival benefit
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Overall response rate |
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Limited clinical relevance Inter- and intra-observer variability Selection bias in exceptional responders or indolent disease, makes measurable disease mandatory Difficult to measure benefit from agents that stabilize the tumor No clear correlation with overall survival benefit
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