SIRFLOX: Progression-Free Survival

About time this was raised formally at ASCO.

http://jco.ascopubs.org/content/early/2016/09/07/JCO.2016.69.3523?ct

In patients with metastatic colorectal cancer, liver metastatic-related complications remain one of the major causes of death.¹ Selective internal radiation therapy (SIRT) is a liver-directed treatment that aims to achieve control of metastatic liver lesions that are not amenable to surgery. Previous studies have shown some activity as a salvage therapy in patients with chemorefractory disease.²
The recent article in Journal of Clinical Oncology by van Hazel et al³ defined its primary end point as progression-free survival (PFS) at any site. Is PFS at any site a valid primary outcome for a liver-directed therapy? PFS at any site is an outcome measure of exposure to systemic treatment in both study groups; not surprisingly, the primary outcome was similar in both groups.
On the contrary, the study intervention, SIRT, had an expected median PFS in the liver of 12.6 v 20.5 months (HR, 0.69; P = .002). Would median PFS in the liver be a valid primary outcome of this study considering a preplanned survival analysis of this outcome in a pooled data analysis from other studies? It is important to validate from the pooled data analysis if PFS in the liver is a surrogate end point for survival for future studies of liver-directed therapy.
Furthermore, several studies have reported on the predictive role of [¹⁸F]fluorodeoxyglucose positron emission tomography and computed tomography (CT) in evaluation of functional response after SIRT^4-9; Wong et al⁹ reported better correlation in functional response using positron emission tomography and CT compared with anatomic changes as measured by CT, and it is imperative to consider incorporating functional tumor response assessment in future studies.