A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy

K Fizazi; A Ulys; L Sengeløv; M Moe; S Ladoire; A Thiery-Vuillemin; A Flechon; A Guida; J Bellmunt; M A Climent; S Chowdhury; H Dumez; M Matouskova; N Penel; S Liutkauskiene; L Stachurski; C N Sternberg; F Baton; N Germann; G Daugaard

doi:10.1093/annonc/mdx487

A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy

K Fizazi, A Ulys, L Sengeløv, M Moe, S Ladoire, A Thiery-Vuillemin, A Flechon, A Guida, J Bellmunt, M A Climent, S Chowdhury, H Dumez, M Matouskova, N Penel, S Liutkauskiene, L Stachurski, C N Sternberg, F Baton, N Germann, G Daugaard

Institut for Klinisk Medicin

9 Citationer (Scopus)

Abstract

Background: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. Patients and methods: Patients were randomly assigned (1: 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. Results: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P=0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). Conclusions: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%.

Originalsprog	Engelsk
Tidsskrift	Annals of Oncology
Vol/bind	28
Udgave nummer	11
Sider (fra-til)	2741-2746
ISSN	0923-7534
DOI	https://doi.org/10.1093/annonc/mdx487
Status	Udgivet - nov. 2017

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10.1093/annonc/mdx487

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Citationsformater

Fizazi, K., Ulys, A., Sengeløv, L., Moe, M., Ladoire, S., Thiery-Vuillemin, A., Flechon, A., Guida, A., Bellmunt, J., Climent, M. A., Chowdhury, S., Dumez, H., Matouskova, M., Penel, N., Liutkauskiene, S., Stachurski, L., Sternberg, C. N., Baton, F., Germann, N., & Daugaard, G. (2017). A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy. Annals of Oncology, 28(11), 2741-2746. https://doi.org/10.1093/annonc/mdx487

A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy. / Fizazi, K; Ulys, A; Sengeløv, L et al.
I: Annals of Oncology, Bind 28, Nr. 11, 11.2017, s. 2741-2746.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Fizazi, K, Ulys, A, Sengeløv, L, Moe, M, Ladoire, S, Thiery-Vuillemin, A, Flechon, A, Guida, A, Bellmunt, J, Climent, MA, Chowdhury, S, Dumez, H, Matouskova, M, Penel, N, Liutkauskiene, S, Stachurski, L, Sternberg, CN, Baton, F, Germann, N & Daugaard, G 2017, 'A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy', Annals of Oncology, bind 28, nr. 11, s. 2741-2746. https://doi.org/10.1093/annonc/mdx487

Fizazi K, Ulys A, Sengeløv L, Moe M, Ladoire S, Thiery-Vuillemin A et al. A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy. Annals of Oncology. 2017 nov.;28(11):2741-2746. doi: 10.1093/annonc/mdx487

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title = "A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy",

abstract = "Background: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. Patients and methods: Patients were randomly assigned (1: 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. Results: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P=0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). Conclusions: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%.",

keywords = "Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Disease Management, Double-Blind Method, Follow-Up Studies, Humans, International Agencies, Male, Middle Aged, Prognosis, Prostatic Neoplasms, Castration-Resistant/drug therapy, Quality of Life, Quinolones/administration & dosage, Survival Rate, Taxoids/administration & dosage, Treatment Outcome",

author = "K Fizazi and A Ulys and L Sengel{\o}v and M Moe and S Ladoire and A Thiery-Vuillemin and A Flechon and A Guida and J Bellmunt and Climent, {M A} and S Chowdhury and H Dumez and M Matouskova and N Penel and S Liutkauskiene and L Stachurski and Sternberg, {C N} and F Baton and N Germann and G Daugaard",

note = "{\textcopyright} The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].",

year = "2017",

month = nov,

doi = "10.1093/annonc/mdx487",

language = "English",

volume = "28",

pages = "2741--2746",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "11",

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TY - JOUR

T1 - A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy

AU - Fizazi, K

AU - Ulys, A

AU - Sengeløv, L

AU - Moe, M

AU - Ladoire, S

AU - Thiery-Vuillemin, A

AU - Flechon, A

AU - Guida, A

AU - Bellmunt, J

AU - Climent, M A

AU - Chowdhury, S

AU - Dumez, H

AU - Matouskova, M

AU - Penel, N

AU - Liutkauskiene, S

AU - Stachurski, L

AU - Sternberg, C N

AU - Baton, F

AU - Germann, N

AU - Daugaard, G

PY - 2017/11

Y1 - 2017/11

N2 - Background: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. Patients and methods: Patients were randomly assigned (1: 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. Results: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P=0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). Conclusions: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%.

AB - Background: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. Patients and methods: Patients were randomly assigned (1: 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. Results: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P=0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). Conclusions: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%.

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Disease Management

KW - Double-Blind Method

KW - Follow-Up Studies

KW - Humans

KW - International Agencies

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Prostatic Neoplasms, Castration-Resistant/drug therapy

KW - Quality of Life

KW - Quinolones/administration & dosage

KW - Survival Rate

KW - Taxoids/administration & dosage

KW - Treatment Outcome

U2 - 10.1093/annonc/mdx487

DO - 10.1093/annonc/mdx487

M3 - Journal article

C2 - 29059273

SN - 0923-7534

VL - 28

SP - 2741

EP - 2746

JO - Annals of Oncology

JF - Annals of Oncology

IS - 11

ER -