Platinum compounds have been tested in a larger number of mostly small to medium sized clinical trials in molecularly unselected prostate cancer patients (pts). Advances in castration-resistant prostate cancer (CRPC) molecular profiling have shown that a significant proportion of pts harbor DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. Our aim was to evaluate the antitumour activity of platinum agents in a contemporaneous mCRPC cohort with or without DNA repair defects.
International, multicenter retrospective database project in 14 centers worldwide. Pts with mCRPC treated with a platinum agent were included. Pts with primary pure small cell carcinoma and/or insufficient outcome data were excluded. For antitumour activity PSA levels at baseline, after 4-, 8- and 12-weeks of therapy (tx) were analyzed as well as soft tissue response and duration of platinum-based chemotherapy. Overall survival (OS) was analyzed by Kaplan Meier method.
A total of 167 pts have been included in this analysis, 33 (20%) received platinum monotherapy, 134 (80%) a platinum combination therapy. Carboplatin was used in 140 (84%), cisplatin in 26 (16%) of pts. Combination tx with etoposise was used in 45 (27%), paclitaxel in 35 (21%) and docetaxel in 28 (17%) of pts. At start of platinum tx median age was 68 years, median PSA 78 ug/l, median ALP 185 U/l, median hemoglobin 103 g/l. The metastatic sites at start of platinum therapy were: bone 84%, lymph node 59% and visceral 60%. Outcome data by DNA repair defect status are summarized in the table.Table: 814P
|Outcome of platinum based tx||DNA repair defects: assessed, present N = 40||DNA repair defects: assessed, not present N = 42||DNA repair defects not assessed N = 85|
|N (%)||N (%)||N (%)|
|PSA decline ≥50%||13/32 (41)||8/23 (35)||24/73 (33)|
|Soft tissue response (PR/CR)||9/32 (28)||7/29 (24)||16/48 (33)|
|median time on platinum tx: months (m), interquartile range (IQR)||2.5m (IQR 1.8-5.9)||2.8m (IQR 1.4 – 4.6)||3.5m (IQR 1.4 – 4.6)|
|OS from start of platinum therapy (m, IQR)||9.1m (IQR 4.8 – NR)||11m (IQR 6.7-22)||12m (IQR 7-29)|
In this retrospective analysis of a contemporary cohort of men with mCRPC and poor prognostic characteristics platinum-based treatment seems to have significant anti-tumor activity irrespective of DNA repair status. Comparison of subgroups is limited by small sample size. Updated analyses will be presented.
Clinical trial identification
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Ethical Committee St. Gallen.
Has not received any funding.
S. Gillessen: Advisory boards (compensated): IDMC, AAA International, Active Biotech AB IDMC, Astellas Pharma, Bayer, Bristol-Myers Squibb, Clovis, Curevac, Dendreon Corporation, Ferring, Innocrin Pharmaceuticals, Janssen Cilag, MaxiVAX SA, Millennium Pharmaceuticals, Orion, Roche, Sanofi Aventis Group; Advisory boards (uncompensated): Astellas Pharma, Bayer, ESSA Pharmaceuticals Corp., Nectar, ProteoMediX, Sanofi; Speakers Bureau (compensated): Janssen, Novartis; Speakers bureau (uncompensated): Astellas Pharma, Janssen, Sanofi Aventis Group; Patent pending patent application for a method for biomarker WO 2009138392 A. H. Suzuki: Steering Committee: ACIS (ARN-509); Lead Principle Investigator: ARASENS (ODM-201); Advisory board: AstraZeneca, Bayer, Janssen, Nihon Medi-Physics, Kissei; Research funding: Takeda, Bayer, Astellas, Daiichi-Sankyo, Pfizer, Nihon Kayaku Ono; Honoraria: Astellas, AstraZeneca, Daiichi Sankyo, Janssen, Pfizer, Novartis, Sanofi, Takeda. A.G. Omlin: Advisory role (compensated, institutional): AstraZeneca, Astellas, Bayer, Janssen, Molecular Partners, MSD, Pfizer, Roche, Sanofi Aventis; Research support (institutional): TEVA, Janssen; Travel support: Astellas, Bayer, Janssen, Sanofi, Aventis. All other authors have declared no conflicts of interest.