Optimal assessment of response in ovarian cancer.

Objective tumor response and progression, measured by standard criteria such as RECIST 1.1, are important measures of change in tumor size that are utilized as endpoints in phase II and III clinical trials. In ovarian cancer, RECIST criteria, which are based on anatomical tumor size, have been supplemented by CA125 response and progression criteria developed by the Gynecologic Cancer InterGroup. CA125 progression has been integrated with objective criteria into a composite definition of progression often used in the front-line setting, whereas response criteria are generally intended for use in recurrent disease trials. In terms of the performance of these endpoints in clinical trials, objective response, when used to assess the activity of new drugs in phase II trials in recurrent ovarian cancer, has proven to be helpful in identifying agents that have subsequently been shown to improve overall or progression-free survival in randomized trials. Thus, objective response has utility as an endpoint for new drug screening trials. Progression-free survival is often used as the primary (or co-primary) efficacy endpoint in studies of first-line therapy in ovarian cancer. Data from historical studies of platinum-based chemotherapy regimens indicate that improvements in progression-free survival generally translate into overall survival gains, indicating it may qualify as a surrogate endpoint for overall survival. It is not yet clear if this relationship will hold true in randomized trials of targeted agents, making it important to continue to assess overall survival in such studies. Finally, the routine monitoring of CA125 in patients after completion of front-line treatment as part of the standard of care has come under question with the publication of the results of a large European study; therefore, the use of CA125 progression as an endpoint in clinical trials will also likely be debated in the coming years.