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PSA response rate as a surrogate marker for median overall survival in docetaxel-based first-line treatments for patients with metastatic castration-resistant prostate cancer: an analysis of 22 trials

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Tumor Biology

Abstract

The aim of this study was to determine the correlation between PSA response rate (PSA RR) and overall survival (OS) and identify PSA RR as a potential surrogate for OS, in docetaxel-based first-line treatments for castration-resistant prostate cancer (CRPC). Trials of first-line regimens with docetaxel for patients with metastatic CRCP published between 2004 and 2013 were identified, and data were evaluated statistically in order to investigate the correlation between PSA RR and OS. A total of 22 trials were identified and included in our analysis, for a total of 7,677 patients. In addition, we divided all the trails and arms of the randomized trials in two subgroups, the first one composed only of docetaxel (D) plus prednisone (P) regimens (standard therapy) and the second one composed of all D + other drug combinations (D combinations). Analysing all the trials and arms as a single unit, we found a statistically significant correlation between PSA RR and OS, with Spearman’s rank correlation coefficient ρ = 0.50 (95 % confidence interval (CI), 0.47 to 0.88) (P = 0.003). Also evaluating the standard therapy group, we found a statistically significant correlation between PSA RR and OS, with Spearman’s ρ = 0.65 (95 % CI, 0.38 to 0.70) (P = 0.02). However, when we assessed the D combination group, we found Spearman’s rank correlation coefficient decreased (ρ = 0.42) (95 % CI, 0.28 to 0.80) and resulted nonstatistically significant (P = 0.06). In conclusion, we found a statistically significant correlation between PSA RR and OS. The usage of PSA RR as a surrogate marker for OS in metastatic CRPC patients treated with D-based first-line regimens may be appropriate only in the D + P combination.

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References

  1. Petrylak DP, Tangen CM, Hussain MH, Lara Jr PN, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513–20.

    Article  CAS  PubMed  Google Scholar 

  2. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.

    Article  CAS  PubMed  Google Scholar 

  3. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–54.

    Article  PubMed  Google Scholar 

  4. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22. doi:10.1056/NEJMoa1001294.

    Article  CAS  PubMed  Google Scholar 

  5. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.

    Article  CAS  PubMed  Google Scholar 

  7. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  CAS  PubMed  Google Scholar 

  9. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014. in press.

  10. Zhang T, Dhawan MS, Healy P, George DJ, et al. Clinical benefit of docetaxel or enzalutamide after progression on first-line abiraterone acetate and prednisone in men with metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol. 2014;32(suppl; abstr e16031).

  11. Scher HI, Morris MJ, Kelly WK, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26(7):1148–59.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Hussain M, Goldman B, Tangen C, et al. Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916. J Clin Oncol. 2009;27(15):2450–6.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Roviello G, Petrioli R, Francini E. Time for a revision on the role of PSA response rate as a surrogate marker for median overall survival in docetaxel-based first-line treatment for patients with metastatic hormone-refractory prostate cancer. Int J Biol Markers. 2013;28(3):326–328

  14. Nelius T, Reiher F, Lindenmeir T, Klatte T, Rau O, Burandt J, et al. Characterization of prognostic factors and efficacy in a phase-II study with docetaxel and estramustine for advanced hormone refractory prostate cancer. Onkologie. 2005;28(11):573–8.

    Article  CAS  PubMed  Google Scholar 

  15. Kolodziej M, Neubauer MA, Rousey SR, Pluenneke RE, Perrine G, Mull S, et al. Phase II trial of docetaxel/capecitabine in hormone-refractory prostate cancer. Clin Genitourin Cancer. 2006;5(2):155–61.

    Article  CAS  PubMed  Google Scholar 

  16. Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, et al. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol. 2007;25(6):669–74.

    Article  CAS  PubMed  Google Scholar 

  17. Machiels JP, Mazzeo F, Clausse M, Filleul B, Marcelis L, Honhon B, et al. Prospective randomized study comparing docetaxel, estramustine, and prednisone with docetaxel and prednisone in metastatic hormone-refractory prostate cancer. J Clin Oncol. 2008;26(32):5261–8.

    Article  CAS  PubMed  Google Scholar 

  18. Dawson NA, Halabi S, Ou SS, Biggs DD, Kessinger A, Vogelzang N, et al. A phase II study of estramustine, docetaxel, and exisulind in patients with hormone- refractory prostate cancer: results of cancer and leukemia group B trial 90004. Clin Genitourin Cancer. 2008;6(2):110–6.

    Article  CAS  PubMed  Google Scholar 

  19. Buch-Hansen TZ, Bentzen L, Hansen S, Hoeyer M, Jensen NV, Saxe C, et al. Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer. Cancer Chemother Pharmacol. 2010;66(2):295–301.

    Article  CAS  PubMed  Google Scholar 

  20. Miura N, Numata K, Kusuhara Y, Shirato A, Hashine K, Sumiyoshi Y. Docetaxel-prednisolone combination therapy for Japanese patients with hormone-refractory prostate cancer: a single institution experience. Jpn J Clin Oncol. 2010;40(11):1092–8.

    Article  PubMed  Google Scholar 

  21. Nakagami Y, Ohori M, Sakamoto N, Koga S, Hamada R, Hatano T, et al. Safety and efficacy of docetaxel, estramustine phosphate and hydrocortisone in hormone-refractory prostate cancer patients. Int J Urol. 2010;17(7):629–34.

    Article  CAS  PubMed  Google Scholar 

  22. Ning YM, Gulley JL, Arlen PM, Woo S, Steinberg SM, Wright JJ, et al. Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(12):2070–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Picus J, Halabi S, Kelly WK, Vogelzang NJ, Whang YE, Kaplan EB, et al. A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate-resistant prostate cancer: results from Cancer and Leukemia Group B Study 90006. Cancer. 2011;117(3):526–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Sonpavde G, Matveev V, Burke JM, Caton JR, Fleming MT, Hutson TE, et al. Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer. Ann Oncol. 2012;23(7):1803–8.

    Article  CAS  PubMed  Google Scholar 

  25. Kelly WK, Halabi S, Carducci M, et al. Randomized, double blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. J Clin Oncol. 2012;30(13):1534–40

  26. Hatano K, Nishimura K, Nakai Y, Yoshida T, Sato M, Kawashima A, et al. Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer. Int J Clin Oncol. 2012;(4):704–10

  27. Meulenbeld HJ, van Werkhoven ED, Coenen JL, Creemers GJ, Loosveld OJ, de Jong PC, et al. Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro). Eur J Cancer. 2012;48(16):2993–3000. doi:10.1016/j.ejca.2012.05.014.

    Article  CAS  PubMed  Google Scholar 

  28. Zurita AJ, George DJ, Shore ND, Liu G, Wilding G, Hutson TE, et al. Sunitinib in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic, castration-resistant prostate cancer: a phase 1/2 clinical trial. Ann Oncol. 2012;23(3):688–94.

    Article  CAS  PubMed  Google Scholar 

  29. Fizazi KS, Higano CS, Nelson JB, Gleave M, Miller K, Morris T, et al. Phase III, randomized, placebo-controlled study of docetaxel in combination with zibotentan in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2013;31(14):1740–7.

    Article  CAS  PubMed  Google Scholar 

  30. Heidenreich A, Rawal SK, Szkarlat K, Bogdanova N, Dirix L, Stenzl A, et al. A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human αν integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2013;24(2):329–36.

    Article  CAS  PubMed  Google Scholar 

  31. Kellokumpu-Lehtinen PL, Harmenberg U, Joensuu T, McDermott R, Hervonen P, Ginman C, et al. 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol. 2013;14(2):117–24.

    Article  CAS  PubMed  Google Scholar 

  32. Tannock IF, Fizazi K, Ivanov S, Karlsson CT, Fléchon A, Skoneczna I, et al. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. Lancet Oncol. 2013;14(8):760–8.

    Article  CAS  PubMed  Google Scholar 

  33. Quinn DI, Tangen CM, Hussain M, Lara Jr PN, Goldkorn A, Moinpour CM, et al. Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial. Lancet Oncol. 2013;14(9):893–900.

    Article  CAS  PubMed  Google Scholar 

  34. Sargent DJ, Wieand HS, Haller DG, et al. Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2005;23:8664–70.

    Article  PubMed  Google Scholar 

  35. Baker SG. Surrogate endpoints: wishful thinking or reality? J Natl Cancer Inst. 2006;98:502–3.

    Article  PubMed  Google Scholar 

  36. Prentice RL. Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med. 1989;8:431–40.

    Article  CAS  PubMed  Google Scholar 

  37. Polascik TJ, Oesterling JE, Partin AW. Prostate specific antigen: a decade of discovery what we have learned and were we are going. J Urol. 1999;162:293–306.

    Article  CAS  PubMed  Google Scholar 

  38. Ornstein DK, Pruthi RS. Prostate-specific antigen. Expert Opin Pharmacother. 2000;1:1399–411.

    Article  CAS  PubMed  Google Scholar 

  39. Sridhara R, Eisenberger MA, Sinibaldi VJ, et al. Evaluation of prostate-specific antigen as a surrogate marker for response of hormonerefractory prostate cancer to suramin therapy. J Clin Oncol. 1995;13:2944–53.

    CAS  PubMed  Google Scholar 

  40. Smith DC, Dunn RL, Stawderman MS, et al. Change in serum prostate-specific antigen as a marker of response to cytotoxic therapy for hormone-refractory prostate cancer. J Clin Oncol. 1998;16:1835–43.

    CAS  PubMed  Google Scholar 

  41. Kelly WK, Scher HI, Mazumdar M, et al. Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer. J Clin Oncol. 1993;11:607–15.

    CAS  PubMed  Google Scholar 

  42. Scher HI, Kelly WK, Zhang ZF, et al. Post-therapy serum prostate-specific antigen level and survival in patients with androgen-independent prostate cancer. J Natl Cancer Inst. 1999;91:244–51.

    Article  CAS  PubMed  Google Scholar 

  43. de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14(19):6302–9.

    Article  PubMed  Google Scholar 

  44. Kamiya N, Suzuki H, Endo T, Yano M, Naoi M, Nishimi D, et al. Clinical usefulness of bone markers in prostate cancer with bone metastasis. Int J Urol. 2012;(11):968–79

  45. Hussain M, Tangen CM, Higano C, et al. Absolute prostate- specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006;24:3984–90.

    Article  PubMed  Google Scholar 

  46. Collette L, Burzykowski T, Carroll KJ, Newling D, Morris T, Schroder FH. Is prostate-specific antigen a valid surrogate endpoint for survival in hormonally treated patients with metastatic prostate cancer? Joint research of the European Organisation for Research and Treatment of Cancer, the Limburgs Universitair Centrum, and AstraZeneca Pharmaceuticals. J Clin Oncol. 2005;23:6139–48.

    Article  PubMed  Google Scholar 

  47. Oosterlinck W, Mattelaer J, Casselman J, Van Velthoven R, Derde MP, Kaufman L. PSA evolution: a prognostic factor during treatment of advanced prostatic carcinoma with total androgen blockade. Data from a Belgian multicentric study of 546 patients. Acta Urol Belg. 1997;65:63–71.

    CAS  PubMed  Google Scholar 

  48. Zhou P, Chen MH, McLeod D, Carroll PR, Moul JW, D’Amico AV. Predictors of prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Clin Oncol. 2005;23:6992–8.

    Article  PubMed  Google Scholar 

  49. Oh WK, Hayes J, Evan C, et al. Development of an integrated prostate cancer research information system. Clin Genitourin Cancer. 2006;5:61–6.

    Article  PubMed  Google Scholar 

  50. Armstrong AJ, Garrett-Mayer E, Ou Yang YC, Carducci MA, Tannock I, de Wit R, et al. Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol. 2007;25(25):3965–70.

    Article  PubMed  Google Scholar 

  51. Petrylak DP, Ankerst DP, Jiang CS, et al. Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16. J Natl Cancer Inst. 2006;98(8):516–21.

    Article  PubMed  Google Scholar 

  52. Hanninen M, Venner P, North S. A rapid PSA half-life following docetaxel chemotherapy is associated with improved survival in hormone refractory prostate cancer. Can Urol Assoc J. 2009;3(5):369–74.

    PubMed Central  PubMed  Google Scholar 

  53. Thomas BM, Smith C, Evans J, Button MR, Kumar S, Palaniappan N, et al. Time to prostate specific antigen (PSA) nadir may predict rapid relapse in men with metastatic castration-resistant prostate cancer (CRPC) receiving docetaxel chemotherapy. Med Oncol. 2013;30(4):719.

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank the two investigators (P.A. and M.S.) for the classification of the data of PSA RR and OS of each trial as significant or nonsignificant for the per-protocol analysis.

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Authors and Affiliations

  1. Medical Oncology Unit, Policlinico Umberto I Hospital, University of Rome, Via del Policlinico 155, 00161, Rome, Italy

    Edoardo Francini

  2. Medical Oncology Unit, University of Siena, Policlinico Le Scotte, Viale Bracci 11, 53100, Siena, Italy

    Roberto Petrioli, Giulia Rossi, Letizia Laera & Giandomenico Roviello

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  1. Edoardo Francini
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  2. Roberto Petrioli
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  3. Giulia Rossi
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  5. Giandomenico Roviello
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Correspondence to Giandomenico Roviello.

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Francini, E., Petrioli, R., Rossi, G. et al. PSA response rate as a surrogate marker for median overall survival in docetaxel-based first-line treatments for patients with metastatic castration-resistant prostate cancer: an analysis of 22 trials. Tumor Biol. 35, 10601–10607 (2014). https://doi.org/10.1007/s13277-014-2559-8

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