Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial

M. Annala; S. Fu; J. V.W. Bacon; J. Sipola; N. Iqbal; C. Ferrario; M. Ong; D. Wadhwa; S. J. Hotte; G. Lo; B. Tran; L. A. Wood; J. R. Gingerich; S. A. North; C. J. Pezaro; J. D. Ruether; S. S. Sridhar; H. M.L. Kallio; D. J. Khalaf; A. Wong; K. Beja; E. Schönlau; S. Taavitsainen; M. Nykter; G. Vandekerkhove; A. A. Azad; A. W. Wyatt; K. N. Chi

doi:10.1016/j.annonc.2021.03.205

Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial

M. Annala
, S. Fu
, J. V.W. Bacon
, J. Sipola
, N. Iqbal
, C. Ferrario
, M. Ong
, D. Wadhwa
, S. J. Hotte
, G. Lo
, B. Tran
, L. A. Wood
, J. R. Gingerich
, S. A. North
, C. J. Pezaro
, J. D. Ruether
, S. S. Sridhar
, H. M.L. Kallio
, D. J. Khalaf
, A. Wong

K. Beja, E. Schönlau, S. Taavitsainen, M. Nykter, G. Vandekerkhove, A. A. Azad, A. W. Wyatt, K. N. Chi^*

^*Tämän työn vastaava kirjoittaja

Tays Syöpäkeskus

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

62 Sitaatiot (Scopus)

Abstrakti

Background: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. Patients and methods: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1: 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50%, radiographic response, or stable disease ≥12 weeks). Results: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). Conclusions: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

Alkuperäiskieli	Englanti
Julkaisu	Annals of Oncology
Vuosikerta	32
Numero	7
DOI - pysyväislinkit	https://doi.org/10.1016/j.annonc.2021.03.205
Tila	Julkaistu - 2021
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

This work was supported by Sanofi , Laval, Quebec, Canada who provided cabazitaxel for use in the study and grant funding for study conduct. Data analysis and correlative studies were funded through research grants from Prostate Cancer Canada, Canadian Institutes of Health Research (CIHR), Movember Foundation, Prostate Cancer Foundation, Terry Fox New Frontiers Program Project Grant [TFF116129], Jane and Aatos Erkko Foundation, and the Academy of Finland (no grant numbers). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. KNC reports honoraria and/or consulting fees from Astellas, AstraZeneca, Constellation Pharmaceuticals, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, Sanofi, and grants and research funding from Astellas, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi. AWW reports a commercial research grant from Janssen and honoraria from AstraZeneca, Astellas, Janssen, and Merck. AAA reports honoraria, consulting fees, and/or research funding from Astellas, AstraZeneca, Janssen, Novartis, Sanofi, Tolmar, Telix, Merck Serono, Bristol Myers Squibb (BMS), Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Aptevo Therapeutics, Glaxo Smith Kline, MedImmune, SYNthorx, Bionomics, Merck Sharpe Dome, and Sanofi Aventis. LAW reports serving on advisory boards (with no personal financial contribution) for Pfizer, EISAI, AstraZeneca, Merck, BMS, and Ipsen, and grants from Pfizer, Merck, AstraZeneca, Roche, and BMS. BT reports grants and personal fees from Amgen, AstraZeneca, BMS, Janssen, Pfizer, MDS, Ipsen and Bayer, grants from Astellas, and personal fees from Sanofi, Tolmar, Novartis, IQVIA, and Roche. All other authors have declared no conflicts of interest.

YK:n kestävän kehityksen tavoitteet

Tämä tuotos edistää seuraavia kestävän kehityksen tavoitteita:

SDG 3 – Hyvä terveys ja hyvinvointi

Julkaisufoorumi-taso

Jufo-taso 2

!!ASJC Scopus subject areas

Hematology
Oncology

Pääsy asiakirjaan

10.1016/j.annonc.2021.03.205

Siteeraa tätä

Annala, M., Fu, S., Bacon, J. V. W., Sipola, J., Iqbal, N., Ferrario, C., Ong, M., Wadhwa, D., Hotte, S. J., Lo, G., Tran, B., Wood, L. A., Gingerich, J. R., North, S. A., Pezaro, C. J., Ruether, J. D., Sridhar, S. S., Kallio, H. M. L., Khalaf, D. J., ... Chi, K. N. (2021). Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial. Annals of Oncology, 32(7). https://doi.org/10.1016/j.annonc.2021.03.205

@article{0fd001f5e06e46739b6ccba31a5e57a3,

title = "Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial",

abstract = "Background: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. Patients and methods: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1: 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50\%, radiographic response, or stable disease ≥12 weeks). Results: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80\% versus 62\%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32\% versus ARPI 0\%), diarrhoea (9\% versus 0\%), infection (9\% versus 0\%), and fatigue (7\% versus 5\%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30\% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). Conclusions: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.",

keywords = "androgen receptor pathway inhibitor, circulating tumor DNA (ctDNA), plasma cell-free DNA, prostate cancer, taxane chemotherapy",

author = "M. Annala and S. Fu and Bacon, \{J. V.W.\} and J. Sipola and N. Iqbal and C. Ferrario and M. Ong and D. Wadhwa and Hotte, \{S. J.\} and G. Lo and B. Tran and Wood, \{L. A.\} and Gingerich, \{J. R.\} and North, \{S. A.\} and Pezaro, \{C. J.\} and Ruether, \{J. D.\} and Sridhar, \{S. S.\} and Kallio, \{H. M.L.\} and Khalaf, \{D. J.\} and A. Wong and K. Beja and E. Sch{\"o}nlau and S. Taavitsainen and M. Nykter and G. Vandekerkhove and Azad, \{A. A.\} and Wyatt, \{A. W.\} and Chi, \{K. N.\}",

note = "Funding Information: This work was supported by Sanofi , Laval, Quebec, Canada who provided cabazitaxel for use in the study and grant funding for study conduct. Data analysis and correlative studies were funded through research grants from Prostate Cancer Canada, Canadian Institutes of Health Research (CIHR), Movember Foundation, Prostate Cancer Foundation, Terry Fox New Frontiers Program Project Grant [TFF116129], Jane and Aatos Erkko Foundation, and the Academy of Finland (no grant numbers). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Funding Information: KNC reports honoraria and/or consulting fees from Astellas, AstraZeneca, Constellation Pharmaceuticals, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, Sanofi, and grants and research funding from Astellas, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi. AWW reports a commercial research grant from Janssen and honoraria from AstraZeneca, Astellas, Janssen, and Merck. AAA reports honoraria, consulting fees, and/or research funding from Astellas, AstraZeneca, Janssen, Novartis, Sanofi, Tolmar, Telix, Merck Serono, Bristol Myers Squibb (BMS), Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Aptevo Therapeutics, Glaxo Smith Kline, MedImmune, SYNthorx, Bionomics, Merck Sharpe Dome, and Sanofi Aventis. LAW reports serving on advisory boards (with no personal financial contribution) for Pfizer, EISAI, AstraZeneca, Merck, BMS, and Ipsen, and grants from Pfizer, Merck, AstraZeneca, Roche, and BMS. BT reports grants and personal fees from Amgen, AstraZeneca, BMS, Janssen, Pfizer, MDS, Ipsen and Bayer, grants from Astellas, and personal fees from Sanofi, Tolmar, Novartis, IQVIA, and Roche. All other authors have declared no conflicts of interest. Publisher Copyright: {\textcopyright} 2021 European Society for Medical Oncology",

year = "2021",

doi = "10.1016/j.annonc.2021.03.205",

language = "English",

volume = "32",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier",

number = "7",

}

Annala, M, Fu, S, Bacon, JVW, Sipola, J, Iqbal, N, Ferrario, C, Ong, M, Wadhwa, D, Hotte, SJ, Lo, G, Tran, B, Wood, LA, Gingerich, JR, North, SA, Pezaro, CJ, Ruether, JD, Sridhar, SS, Kallio, HML, Khalaf, DJ, Wong, A, Beja, K, Schönlau, E, Taavitsainen, S , Nykter, M, Vandekerkhove, G, Azad, AA, Wyatt, AW & Chi, KN 2021, 'Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial', Annals of Oncology, Vuosikerta 32, Nro 7. https://doi.org/10.1016/j.annonc.2021.03.205

TY - JOUR

T1 - Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer

T2 - a multicentre, randomised, open-label, phase II trial

AU - Annala, M.

AU - Fu, S.

AU - Bacon, J. V.W.

AU - Sipola, J.

AU - Iqbal, N.

AU - Ferrario, C.

AU - Ong, M.

AU - Wadhwa, D.

AU - Hotte, S. J.

AU - Lo, G.

AU - Tran, B.

AU - Wood, L. A.

AU - Gingerich, J. R.

AU - North, S. A.

AU - Pezaro, C. J.

AU - Ruether, J. D.

AU - Sridhar, S. S.

AU - Kallio, H. M.L.

AU - Khalaf, D. J.

AU - Wong, A.

AU - Beja, K.

AU - Schönlau, E.

AU - Taavitsainen, S.

AU - Nykter, M.

AU - Vandekerkhove, G.

AU - Azad, A. A.

AU - Wyatt, A. W.

AU - Chi, K. N.

N1 - Funding Information: This work was supported by Sanofi , Laval, Quebec, Canada who provided cabazitaxel for use in the study and grant funding for study conduct. Data analysis and correlative studies were funded through research grants from Prostate Cancer Canada, Canadian Institutes of Health Research (CIHR), Movember Foundation, Prostate Cancer Foundation, Terry Fox New Frontiers Program Project Grant [TFF116129], Jane and Aatos Erkko Foundation, and the Academy of Finland (no grant numbers). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Funding Information: KNC reports honoraria and/or consulting fees from Astellas, AstraZeneca, Constellation Pharmaceuticals, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, Sanofi, and grants and research funding from Astellas, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi. AWW reports a commercial research grant from Janssen and honoraria from AstraZeneca, Astellas, Janssen, and Merck. AAA reports honoraria, consulting fees, and/or research funding from Astellas, AstraZeneca, Janssen, Novartis, Sanofi, Tolmar, Telix, Merck Serono, Bristol Myers Squibb (BMS), Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Aptevo Therapeutics, Glaxo Smith Kline, MedImmune, SYNthorx, Bionomics, Merck Sharpe Dome, and Sanofi Aventis. LAW reports serving on advisory boards (with no personal financial contribution) for Pfizer, EISAI, AstraZeneca, Merck, BMS, and Ipsen, and grants from Pfizer, Merck, AstraZeneca, Roche, and BMS. BT reports grants and personal fees from Amgen, AstraZeneca, BMS, Janssen, Pfizer, MDS, Ipsen and Bayer, grants from Astellas, and personal fees from Sanofi, Tolmar, Novartis, IQVIA, and Roche. All other authors have declared no conflicts of interest. Publisher Copyright: © 2021 European Society for Medical Oncology

PY - 2021

Y1 - 2021

N2 - Background: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. Patients and methods: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1: 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50%, radiographic response, or stable disease ≥12 weeks). Results: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). Conclusions: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

AB - Background: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. Patients and methods: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1: 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50%, radiographic response, or stable disease ≥12 weeks). Results: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). Conclusions: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

KW - androgen receptor pathway inhibitor

KW - circulating tumor DNA (ctDNA)

KW - plasma cell-free DNA

KW - prostate cancer

KW - taxane chemotherapy

U2 - 10.1016/j.annonc.2021.03.205

DO - 10.1016/j.annonc.2021.03.205

M3 - Article

C2 - 33836265

AN - SCOPUS:85105110200

SN - 0923-7534

VL - 32

JO - Annals of Oncology

JF - Annals of Oncology

IS - 7

ER -

Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial

Abstrakti

Rahoitus

YK:n kestävän kehityksen tavoitteet

Julkaisufoorumi-taso

!!ASJC Scopus subject areas

Pääsy asiakirjaan

Sormenjälki

Siteeraa tätä