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 sessionZUMA-3: A phase 1/2 multi-center study evaluation the safety and efficacy of KTE-C19 anti-CD19 CAR T cells in adult patients with relapsed/refractory B precursor acute lymphoblastic leukemia (R/R ALL)Presenter: Bijal Shah Session: Poster display Resources: Abstract ZUMA-2: A phase 2 multi-center study evaluating the efficacy of KTE-C19 (Anti-CD19 CAR T cells) in patients with relapsed/refractory Mantle cell lymphoma (R/R MCL)Presenter: Michael Wang Session: Poster Display Resources: Abstract ZUMA-1: A phase 2 multi-center study evaluating anti-CD19 chimeric antigen receptor (CAR) T cells in patients with refractory aggressive non-Hodgkin lymphoma (NHL)Presenter: Sattva Neelapu Session: Poster Display Resources: Abstract Younger age as a prognostic indicator in breast cancer: Correlation between clinical-pathologic factors and miRNAs and long-term follow-upPresenter: Maria Teresa Martinez Session: Poster display Resources: Abstract Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)Presenter: Christy Toms Session: Poster display Resources: Abstract Whole exome sequencing (WES) and RNA sequencing (RNA-seq) in routine clinical practice for colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) patients (pts)Presenter: Géraldine Perkins Session: Poster display Resources: Abstract What is the optimal annual interpretive volume for a radiologist reading screening mammograms?Presenter: Asli Uluturk Session: Poster display Resources: Abstract What decides breast conservation versus mastectomy in the background of diverse sociocultural environment, an Indian studyPresenter: Poonamalle Padmanabhan Bapsy Session: Poster display Resources: Abstract Waiting time to diagnosis and treatment of the head and neck cancer in four institutions in PortugalPresenter: Ana Castro Session: Poster display Resources: Abstract Wait times for diagnosis and treatment of lung cancer: a single centre experiencePresenter: Catherine Labbe 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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