Radiographic progression without PSA progression in advanced prostate cancer patients.

Abstract

213 Background: Androgen Receptor Pathway Inhibitors (ARPIs) are frequently combined with Androgen Deprivation Therapy (ADT) to treat prostate cancer patients (pts) with castration sensitive (CSPC) or castration resistant (CRPC) disease. We sought to characterize pts who experienced radiographic progression without PSA progression (R-PD) while under treatment with ADT with or without an ARPI. Methods: We undertook a retrospective analysis of two phase 3 trials testing apalutamide (Apa) + ADT vs Placebo (Pbo) + ADT: TITAN (NCT02489318) in pts with metastatic CSPC (mCSPC) and SPARTAN (NCT01946204) in pts with non-metastatic CRPC (nmCRPC). We compared pts with R-PD with pts who experienced PSA progression before or concurrently with radiographic progression (PSA-PD). Kaplan-Meier and Cox proportional-hazard models were used to estimate time-to-event and hazard ratios. Results: The distribution of types of progression, and location of R-PD by study is shown in the table. Pts with R-PD had shorter overall survival (OS) compared with PSA-PD pts in both studies (median OS R-PD vs PSA-PD: 22.9 m vs 37.4 m in TITAN; 49.8 m vs 53.7 m in SPARTAN). Compared with Pbo, Apa delayed the time to R-PD in both studies (HR 0.51, 95% CI: 0.36 to 0.73 in TITAN; HR 0.17, 95% CI: 0.1 to 0.28 in SPARTAN). No pre-treatment variables predictive of R-PD vs PSA-PD were identified; transcriptional profile analysis is ongoing. Conclusions: Radiographic progression in the absence of PSA progression is not uncommon amongst patients with advanced prostate cancer, and carries a poor prognosis. The addition of Apa prolongs the median time to R-PD. Our findings underscore the importance of monitoring these pts with imaging, independent of PSA dynamics. The impaired survival of R-PD pts warrants evaluation of new therapeutic approaches for these pts. OVERALL TITAN (mCSPC; n=1052) SPARTAN (nmCRPC; n=1207) % pts with R-PD 12.4% 10.4% % pts with PSA-PD 41.2% 45.4% Sites of progression in R-PD pts (% of randomized pts) Bone only 6.3% 1% Non-bone 6% 8.8% Both 0.1% 0%