Patients with metastatic castration-resistant prostate cancer (mCRPC) are primary resistant (PR) to the new agent (NA)-based second line: Clinical outcomes and prognostic factors of subsequent treatment with another NA.

e585 Background: Several NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] changed the prognosis of mCRPC pts being able to significantly prolong their overall survival (OS) after docetaxel failure. Unfortunately, a quote of pts experiences an early progression (within 3 mos) during the second line treatment and it is unclear if a clinical benefit may result from a subsequent treatment with another NA. The present study is aimed to assess the clinical outcomes and prognostic factors of subsequent NA treatment in those pts PR to the second line NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. For the purpose of the present analysis we consider as PR pts who progressed within 3 months from the start of the NA second line. Cox regression analysis was used to assess the independent prognostic value of a series of third-line baseline covariates, in terms of progression free survival (PFS) and OS. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. The NA-based second line consisted of AA (261 pts), CABA (151), and ENZ (64): we identified 55 PR pts (AA 24 – CABA 24 – ENZ 7). All pts received a subsequent NA-based third line: 22 received AA, 25 CABA, and 8 ENZ. Compared to no-PR pts, PR pts showed a lower biochemical response rate (12.2% vs 31.6%; p = 0.005), but no significant differences in terms of objective response rate (17.1% vs 15.2%), PFS (median 3.5 vs 4.7 mos), and OS (median 9.4 vs 12.9 mos). Considering the PR population, at the multivariate analysis , lactate dehydrogenase and PSA were independent prognostic factors for PFS in third line, while hemoglobin, PSA, administration of one NA in fourth line and lactate dehydrogenase were independent prognostic factors for OS. Conclusions: In our experience, NA-based third line is active also in mCRPC PR population and some factors may help in selecting patients with higher probability of achieving a disease control.