Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials

K. Fizazi; T. W. Flaig; M. Stöckle; H. I. Scher; J. S. de Bono; D. E. Rathkopf; C. J. Ryan; T. Kheoh; J. Li; M. B. Todd; T. W. Griffin; A. Molina; C. H. Ohlmann

doi:10.1093/annonc/mdv545

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials

K. Fizazi, T. W. Flaig, M. Stöckle, H. I. Scher, J. S. de Bono, D. E. Rathkopf, C. J. Ryan, T. Kheoh, J. Li, M. B. Todd, T. W. Griffin, A. Molina, C. H. Ohlmann

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. Patients and methods: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. Results: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostatespecific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. Conclusion: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. Clinical trials number: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).

Original language	English (US)
Pages (from-to)	699-705
Number of pages	7
Journal	Annals of Oncology
Volume	27
Issue number	4
DOIs	https://doi.org/10.1093/annonc/mdv545
State	Published - Apr 1 2016

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Publisher Copyright:
© The Author 2015.

Keywords

Abiraterone acetate
Chemotherapy-naïve
Gleason score
Post-chemotherapy
Prostate cancer

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Fizazi, K., Flaig, T. W., Stöckle, M., Scher, H. I., de Bono, J. S., Rathkopf, D. E., Ryan, C. J., Kheoh, T., Li, J., Todd, M. B., Griffin, T. W., Molina, A., & Ohlmann, C. H. (2016). Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials. Annals of Oncology, 27(4), 699-705. https://doi.org/10.1093/annonc/mdv545

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials. / Fizazi, K.; Flaig, T. W.; Stöckle, M. et al.
In: Annals of Oncology, Vol. 27, No. 4, 01.04.2016, p. 699-705.

Research output: Contribution to journal › Article › peer-review

Fizazi, K, Flaig, TW, Stöckle, M, Scher, HI, de Bono, JS, Rathkopf, DE, Ryan, CJ, Kheoh, T, Li, J, Todd, MB, Griffin, TW, Molina, A & Ohlmann, CH 2016, 'Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials', Annals of Oncology, vol. 27, no. 4, pp. 699-705. https://doi.org/10.1093/annonc/mdv545

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title = "Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials",

abstract = "Background: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. Patients and methods: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-na{\"i}ve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. Results: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-na{\"i}ve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostatespecific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. Conclusion: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. Clinical trials number: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).",

keywords = "Abiraterone acetate, Chemotherapy-na{\"i}ve, Gleason score, Post-chemotherapy, Prostate cancer",

author = "K. Fizazi and Flaig, {T. W.} and M. St{\"o}ckle and Scher, {H. I.} and {de Bono}, {J. S.} and Rathkopf, {D. E.} and Ryan, {C. J.} and T. Kheoh and J. Li and Todd, {M. B.} and Griffin, {T. W.} and A. Molina and Ohlmann, {C. H.}",

note = "Publisher Copyright: {\textcopyright} The Author 2015.",

year = "2016",

month = apr,

day = "1",

doi = "10.1093/annonc/mdv545",

language = "English (US)",

volume = "27",

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TY - JOUR

T1 - Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials

AU - Fizazi, K.

AU - Flaig, T. W.

AU - Stöckle, M.

AU - Scher, H. I.

AU - de Bono, J. S.

AU - Rathkopf, D. E.

AU - Ryan, C. J.

AU - Kheoh, T.

AU - Li, J.

AU - Todd, M. B.

AU - Griffin, T. W.

AU - Molina, A.

AU - Ohlmann, C. H.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. Patients and methods: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. Results: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostatespecific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. Conclusion: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. Clinical trials number: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).

AB - Background: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. Patients and methods: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. Results: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostatespecific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. Conclusion: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. Clinical trials number: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).

KW - Abiraterone acetate

KW - Chemotherapy-naïve

KW - Gleason score

KW - Post-chemotherapy

KW - Prostate cancer

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U2 - 10.1093/annonc/mdv545

DO - 10.1093/annonc/mdv545

M3 - Article

C2 - 26609008

AN - SCOPUS:84964690889

SN - 0923-7534

VL - 27

SP - 699

EP - 705

JO - Annals of Oncology

JF - Annals of Oncology

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ER -

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials

Abstract

Bibliographical note

Keywords

UN SDGs

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