Lara, Primo;
Ely, Benjamin;
Quinn, David I.;
Tangen, Catherine M.;
Gertz, Erik;
Mack, Philip C.;
Twardowski, Przemyslaw;
Vogelzang, Nicholas J.;
Hussain, Maha;
Thompson, Ian Murchie;
Van Loan, Marta
SWOG 0421: Prognostic and predictive value of bone metabolism biomarkers (BMB) in castration resistant prostate cancer (CRPC) patients (pts) with skeletal metastases treated with docetaxel (DOC) with or without atrasentan (ATR)
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Media type:
E-Article
Title:
SWOG 0421: Prognostic and predictive value of bone metabolism biomarkers (BMB) in castration resistant prostate cancer (CRPC) patients (pts) with skeletal metastases treated with docetaxel (DOC) with or without atrasentan (ATR)
Contributor:
Lara, Primo;
Ely, Benjamin;
Quinn, David I.;
Tangen, Catherine M.;
Gertz, Erik;
Mack, Philip C.;
Twardowski, Przemyslaw;
Vogelzang, Nicholas J.;
Hussain, Maha;
Thompson, Ian Murchie;
Van Loan, Marta
imprint:
American Society of Clinical Oncology (ASCO), 2012
Description:
<jats:p> 4547 </jats:p><jats:p> Background: S0421, a phase III study of DOC +/- the endothelin antagonist ATR in CRPC pts with bone metastases, showed no overall survival (OS) benefit for DOC+ATR. While BMB may have a prognostic role in CRPC, their predictive role vis a vis bone-targeted therapy such as ATR is unknown. We prospectively assessed pre-treatment serum BMB from S0421 pts to validate their prognostic and predictive value. Methods: BMB for resorption (N-telopeptide, NTX and Pyridinoline, PYD) and formation (C-terminal collagen propeptide, CICP and bone alkaline phosphatase, BAP) were assayed [Quidel (PYD, CICP, BAP) and Wampole (NTX)]. Cox regression models for OS based on BMB adjusted for clinical variables were developed. An adjusted Cox model was fit with main effects and BMB x Treatment interaction to assess predictive value of ATR on OS. Results: Of 1,038 pts, 855 (82%) submitted baseline serum: 778 (91%) were usable and analyzable. Pt characteristics: median age = 69 years; PS 0-1 = 91%, Bisphosphonate use = 61%; Gleason >7 = 56%; median PSA = 68; and bone mets only = 45%. BMB values (median; range): NTX (14 nM; 9.3-23.9), BAP (64.7 u/L; 35-164), CICP (9.5 ng/mL; 6.5-17.4), and PYD (2.8 nmol/L; 2.2-3.9). Table below shows prognostic role of BMB. Pts with very high BMB (upper 25 %ile, n=47) not only have poor prognosis (HR = 4.3, p<0.001) but have OS benefit from ATR (HR=0.34, median OS = 13.6 vs. 6.7 months; interaction p=0.002**). Conclusions: S0421 validates the strong independent OS prognostic value of BMB in CRPC. Very high BMB levels appear to be significantly predictive of OS benefit with ATR. Further study of endothelin antagonists in CRPC should focus on this high-risk pt subset. (5R01-CA120469) [Table: see text] </jats:p>