According to an analysis of the PREVAIL and AFFIRM clinical trials, development of new bone lesions in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) who are stable or responding to enzalutamide is a form of pseudoprogression that does not necessarily impact long-term outcomes. The study evaluated outcomes in 1672 patients treated with enzalutamide on these 2 phase III trials. Development of early or late unconfirmed lesions by bone scan did not impact radiographic progression-free survival (rPFS) or overall survival (OS) in chemotherapy-naive men treated on the PREVAIL trial. Among chemotherapy-treated patients on the AFFIRM trial, new lesions did not impact rPFS, but were associated with a reduction in median OS. In both trials, quality of life was not impacted by the development of detectable new bone lesions.
High Altitude: This study highlights the importance of carefully defining markers of response and of true progression both in the clinical trial setting and in clinical practice. In chemotherapy-naive patients, detection of new bone lesions in patients who are otherwise showing no signs of progression during enzalutamide treatment should likely not be considered a sign of progression, whereas new bone lesions are more likely to represent true progression in chemotherapy-pretreated patients. This is an important consideration for the design and interpretation of further studies of enzalutamide and for the development of guidance materials for clinical decision-making.
Ground Level: Community oncologists may find the information in this report of interest when evaluating signs of progression in their patients with mCRPC. While some oncologists may see new lesions as a sign of progression and discontinue enzalutamide, this analysis suggests that new bone lesions alone have limited impact on outcomes in chemotherapy-naive patients and do not indicated true progression in the absence of other symptoms. It will be important, however, to consider treatment history when making this decision, as new bone lesions do appear to be important clinical events in patients who have been previously treated with docetaxel.