Abstract 1113
Background
Skeletal metastasis is seen in most CRPC patients and is a common source of morbidity. We previously reported that bone biomarkers in CRPC patients are independently prognostic for OS, and that in men with highly elevated markers there is benefit from bone-targeted therapy (Lara, et al. JNCI 2014). Here we report our prospectively planned classification & regression tree (CART) analysis of clinical covariates and bone biomarkers as part of the phase III S0421 trial of docetaxel +/- atrasentan.
Methods
Markers for bone resorption [N-telopeptide (NTx) & pyridinoline (PYD)] & formation [C-terminal collagen propeptide (CICP) & bone alkaline phosphatase (BAP)] were measured in pre-treatment sera from men on S0421. Bone biomarkers & baseline clinical covariates were included in a Cox model for OS; significant variables were allowed to compete in a CART analysis to identify prognostic groups using CTREE in the R package "party". Hazard ratios (HR) were calculated by comparing OS in each of the terminal nodes to a reference group in a Cox PH model. Kaplan Meier curves for each prognostic group defined by the tree were constructed.
Results
750 men with evaluable bone marker & clinical data were included. Each bone marker significantly contributed to the final Cox model, with higher levels associated with worse OS. Cox stepwise selection identified BAP, CICP, PYD, hemoglobin (Hgb), pain score, age, black race, PSA, and visceral disease as associated with OS. CART analysis selected CICP, BAP, Hgb, & pain score for the final model, & identified 5 prognostic groups:
| Prognostic Group | Description | N | Median OS (months) | Hazard Ratio (95% CI) | p-value |
|---|---|---|---|---|---|
| 1 | Hgb 11.3 CICP 6.8 Worst pain > =4 | 144 | 15.3 | 0.79 (0.63, 0.99) | 0.04 |
| 4 | Hgb > 11.3 CICP > 6.8 Worst pain ConclusionsElevated serum levels of bone biomarkers are strongly associated with worse OS in CRPC. CART analysis incorporating bone biomarkers identified five distinct prognostic CRPC groups with differential OS outcomes. These results further define & establish the role of bone biomarkers in the design and conduct of CRPC clinical trials. Clinical trial identificationClinicalTrials.gov NCT00134056; NCI 5R01-CA120469, CA180888 and CA180819 Legal entity responsible for the studySouthwest Oncology Group (SWOG) and the University of California Davis FundingNational Cancer Institute (USA) DisclosureP.N. Lara: In the past 3 years I have served as a consultant (advisory board or DSMC member) for Clovis, Exelixis, Pfizer, Teva, Halozyme, Novartis, Sanofi, LPath, Lilly, Astra Zeneca, Bayer, and Genentech/Roche. D.I. Quinn: Sanofi, Astellas, and Bayer for honoraria (ad boards) and Dendreon and Sanofi for trial support. All other authors have declared no conflicts of interest. Resources from the same session2354 - The clinicopathologic features and treatment of 607 hindgut neuroendocrine tumor (NET) patients at a single institutionPresenter: Seung Tae Kim Session: Poster Display Resources: Abstract 2594 - Neuroendocrine carcinomas of the colorectal origin - Polish experiencePresenter: Agnieszka Kolasińska-Ćwikła Session: Poster Display Resources: Abstract 2539 - Neuroendocrine neoplasms of the appendix including goblet cell carcinoidsPresenter: Agnieszka Kolasinska-Cwikla Session: Poster Display Resources: Abstract 1245 - Prognostic validity of AJCC staging system in neuroendocrine tumors of the appendixPresenter: Amir Mehrvarz Sarshekeh Session: Poster Display Resources: Abstract 3902 - Enhancer of zest homolog 2 (EZH2) expression in well and moderately differentiated pancreatic neuroendocrine tumor (pNET)Presenter: Riccardo Marconcini Session: Poster Display Resources: Abstract 3882 - Differential clinical and pathological characteristics of hereditary neuroendocrine pancreatic tumours (NEPT)Presenter: Gema Marín Zafra Session: Poster Display Resources: Abstract 2296 - Natural course of thyroid cancer nodules compared with benign thyroid nodulesPresenter: Kyung-Jin Yun Session: Poster Display Resources: Abstract 4083 - Reassessment of proliferative activity at disease progression in neuroendocrine neoplasmsPresenter: Noemi Cicchese Session: Poster Display Resources: Abstract 3866 - 18F-FDG-PET to predict disease progression in advanced digestive neuroendocrine neoplasmsPresenter: Maria Rinzivillo Session: Poster Display Resources: Abstract 3651 - UK phase IV, observational study to assess quality of life in patients (pts) with pancreatic neuroendocrine tumours (pNETS) receiving treatment with everolimus: The “real-world” OBLIQUE studyPresenter: John Ramage Session: Poster Display Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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