Predictors of response to platinum (Pt)-based chemotherapy in metastatic castration-resistant prostate cancer (mCRPC).

Abstract

e575 Background: Aggressive variant PC (AVPC) is a well-described subtype of PC which portends a poor prognosis. Studies have shown an increase in progression-free survival(PFS) when Pt is added to taxane-based treatment in AVPC. Clinical features including visceral metastasis, lytic bone lesions, low PSA, short responses to androgen suppression and high Gleason score at diagnosis predict response to upfront docetaxel (D) and Pt (Aparicio et. al. Clin Cancer Res 2013). Our objective was to study the effect of baseline characteristics on PFS with D+Pt in D-pretreated CRPC. Methods: A retrospective review of D-pretreated mCRPC men who received D (60-75 mg/m2) and carboplatin (C, AUC 4-5) at our institution between 2008- 2015 were included in this analysis. All patients had metastatic CRPC, were heavily pre- treated (median treatments = 4) and received at least one cycle of D+C. Numerical data was analyzed using Student’s T-test; binary data was analyzed with Z-proportions test. Results: 28 patients were identified. The median age was 60 yrs(48-73); median PSA at diagnosis was 21ng/dl(0.3-5000); median PSA at the start of D+C was 115.32 ng/dl( 0.65-1395). The response rate was 60.7% and the median time to response was 1 mo. The median reduction in PSA was 48.13%. The median PFS was 6 mo, and median OS was 10 mo. Common treatment – related side effects included grade 1 fatigue (82.14%), pancytopenia (42.86%), and febrile neutropenia (10.71%). Correlation of baseline characteristics to PFS was evaluated. Short response to ADT < 1 yr (p < 0.05), prior response to D (PFS > 6 months) ( p = 0.037), and presence of visceral mets (p < 0.05) predicted better response to D+C. Age (p = 0.27), Gleason score at diagnosis (p = 0.08), performance status at start of therapy (p = 0.27), PSA at diagnosis (p = 0.35), and PSA at start of D+C (p = 0.420) did not predict response. Conclusions: D+C is effective and safe in D pretreated CRPC. Response to prior D, short response to ADT, and the presence of visceral metastasis predicted response to D+C. These are features of AVPC. Prospective studies to validate our findings and identify molecular characteristics of Pt responders are needed in this heavily pre-treated “real world” patient population.