The Waning Relationship Between Progression-Free Survival and Overall Survival in Randomized Cancer Therapy Trials

The availability in an increasing percentage of malignancies of a number of active antineoplastic drug strategies has created a situation in which a statistically significant favorable impact of a given anticancer regimen on the time to disease progression in a randomized trial may not be shown to translate into a similar influence on overall survival (OS). This outcome is due to the benefits associated with the uncontrolled, but ethically required, delivery of one or more of these standard-of-care regimens to potentially all trial participants following their removal from the study in question. As a result, it would be highly inappropriate to conclude that a non-statistically significant OS outcome in a randomized trial is evidence for the lack of clinical utility of an investigative approach that has been documented to improve progression-free survival.