Patients with metastatic prostate cancer enrolled in phase 1 trials: Outcomes and molecular alterations

Abstract

Background: The purpose was to described characteristics of patients ( pts) with castration-resistant prostate cancer (CRPC) referred to phase I unit for phase I trials or molecular screening programs. Methods: All patients enrolled in clinical trials in the Gustave Roussy phase I unit (DITEP) from 2006 until April 2016 were reviewed. Baseline characteristics, PSA response, progression-free survival (PFS) and overall survival (OS) were investigated. Molecular alterations (MA) were collected from MOSCATO trial database comprising 1168 patients screened for genomic characterization. Results: Ninety-three pts had CRPC, enrolled in 30 different trials. At baseline, median age was 68.5y (63.5 - 73.0), 62 pts (66.7%) had an OMS PS 1, median PSA was 96 (32.9 - 369) ng/mL, median albumin 37 (35 - 39) g/L, median ALP 102 (72 - 178), median hemoglobin 11.9 (10.9 - 13.0) g/dL. Nineteen (20.4%) patients had a Royal Marsden Hospital Score of 2 to 3, 14 (15.1%) patients were chemo-naive and 25 (26.9%) had visceral metastases. The median number of previous treatments was 3 (range 0 - 7). Concerning efficacy, 27 (29%) pts had biological response (PSA decrease >50%) and 6 of them had a very good biological response (PSA decrease >90%). Among the cohort, PFS was 3.8 months (2.96 - 4.64) and OS 21.27 months (12.6 - 29.9). Factors significantly associated with OS were RMH score (HR 1.54; 95CI 1.13 - 2.09), number of previous lines of treatment (HR 1.40; 95CI 1.12 - 1.76), and Hemoglobin (HR 0.96; 95CI 0.92 - 0.99). Among patients screened for genomic characterization, 71 had CRPC and 33 (46,5%) were enrolled in phase I trials. MA were found in 49 (69%) of them. Most frequent MA found were : PTEN loss (63.3%), Androgen Receptor amplification or mutation (44.9%), PI3K mutation (22.4%), FGFR and MYC mutation (16.3%). Five pts (10.2%) had BRCA alterations. Ten patients were treated with a matched targeted therapy regarding their molecular alteration. Conclusions: In our cohort of prostate cancer enriched population enrolled in phase I trials, not only RMS but the previous number of lines and hemoglobin should be taken into account to estimate OS. Moreover, targetable molecular alterations are frequently identified in advanced CRPC patients.