Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

Matthew R. Smith, Fred Saad, Simon Chowdhury, Stéphane Oudard, Boris A. Hadaschik, Julie N. Graff, David Olmos, Paul N. Mainwaring, Ji Youl Lee, Hiroji Uemura, Angela Lopez-Gitlitz, Géralyn C. Trudel, Byron M. Espina, Youyi Shu, Youn C. Park, Wayne R. Rackoff, Margaret K. Yu, Eric J. Small, SPARTAN Investigators

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    Abstract

    Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.

    Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.

    Results: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).

    Conclusions: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.

    Original languageEnglish
    Pages (from-to)1408-1418
    Number of pages11
    JournalNew England Journal of Medicine
    Volume378
    Issue number15
    DOIs
    Publication statusPublished - 12 Apr 2018

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    Prostatic Neoplasms
    Placebos
    Neoplasm Metastasis
    Survival
    Castration
    Therapeutics
    Random Allocation
    Confidence Intervals
    Androgen Receptors
    Prostate-Specific Antigen
    Hypothyroidism
    Exanthema
    Androgens

    Cite this

    Smith, M. R., Saad, F., Chowdhury, S., Oudard, S., Hadaschik, B. A., Graff, J. N., ... SPARTAN Investigators (2018). Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. New England Journal of Medicine, 378(15), 1408-1418. https://doi.org/10.1056/NEJMoa1715546
    Smith, Matthew R. ; Saad, Fred ; Chowdhury, Simon ; Oudard, Stéphane ; Hadaschik, Boris A. ; Graff, Julie N. ; Olmos, David ; Mainwaring, Paul N. ; Lee, Ji Youl ; Uemura, Hiroji ; Lopez-Gitlitz, Angela ; Trudel, Géralyn C. ; Espina, Byron M. ; Shu, Youyi ; Park, Youn C. ; Rackoff, Wayne R. ; Yu, Margaret K. ; Small, Eric J. ; SPARTAN Investigators. / Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. In: New England Journal of Medicine. 2018 ; Vol. 378, No. 15. pp. 1408-1418.
    @article{80ea5d7bf5f249088b61a5599c0d01a8,
    title = "Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer",
    abstract = "Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.Results: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95{\%} confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95{\%} CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6{\%} in the apalutamide group and 7.0{\%} in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8{\%} vs. 5.5{\%}), hypothyroidism (8.1{\%} vs. 2.0{\%}), and fracture (11.7{\%} vs. 6.5{\%}).Conclusions: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.",
    author = "Smith, {Matthew R.} and Fred Saad and Simon Chowdhury and St{\'e}phane Oudard and Hadaschik, {Boris A.} and Graff, {Julie N.} and David Olmos and Mainwaring, {Paul N.} and Lee, {Ji Youl} and Hiroji Uemura and Angela Lopez-Gitlitz and Trudel, {G{\'e}ralyn C.} and Espina, {Byron M.} and Youyi Shu and Park, {Youn C.} and Rackoff, {Wayne R.} and Yu, {Margaret K.} and Small, {Eric J.} and {SPARTAN Investigators} and Ghulam Nabi",
    note = "Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204.",
    year = "2018",
    month = "4",
    day = "12",
    doi = "10.1056/NEJMoa1715546",
    language = "English",
    volume = "378",
    pages = "1408--1418",
    journal = "New England Journal of Medicine",
    issn = "0028-4793",
    publisher = "Massachusetts Medical Society",
    number = "15",

    }

    Smith, MR, Saad, F, Chowdhury, S, Oudard, S, Hadaschik, BA, Graff, JN, Olmos, D, Mainwaring, PN, Lee, JY, Uemura, H, Lopez-Gitlitz, A, Trudel, GC, Espina, BM, Shu, Y, Park, YC, Rackoff, WR, Yu, MK, Small, EJ & SPARTAN Investigators 2018, 'Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer' New England Journal of Medicine, vol. 378, no. 15, pp. 1408-1418. https://doi.org/10.1056/NEJMoa1715546

    Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. / Smith, Matthew R.; Saad, Fred; Chowdhury, Simon; Oudard, Stéphane; Hadaschik, Boris A.; Graff, Julie N.; Olmos, David; Mainwaring, Paul N.; Lee, Ji Youl; Uemura, Hiroji; Lopez-Gitlitz, Angela; Trudel, Géralyn C.; Espina, Byron M.; Shu, Youyi; Park, Youn C.; Rackoff, Wayne R.; Yu, Margaret K.; Small, Eric J.; SPARTAN Investigators.

    In: New England Journal of Medicine, Vol. 378, No. 15, 12.04.2018, p. 1408-1418.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

    AU - Smith, Matthew R.

    AU - Saad, Fred

    AU - Chowdhury, Simon

    AU - Oudard, Stéphane

    AU - Hadaschik, Boris A.

    AU - Graff, Julie N.

    AU - Olmos, David

    AU - Mainwaring, Paul N.

    AU - Lee, Ji Youl

    AU - Uemura, Hiroji

    AU - Lopez-Gitlitz, Angela

    AU - Trudel, Géralyn C.

    AU - Espina, Byron M.

    AU - Shu, Youyi

    AU - Park, Youn C.

    AU - Rackoff, Wayne R.

    AU - Yu, Margaret K.

    AU - Small, Eric J.

    AU - SPARTAN Investigators

    AU - Nabi, Ghulam

    N1 - Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204.

    PY - 2018/4/12

    Y1 - 2018/4/12

    N2 - Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.Results: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).Conclusions: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.

    AB - Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.Results: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).Conclusions: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.

    U2 - 10.1056/NEJMoa1715546

    DO - 10.1056/NEJMoa1715546

    M3 - Article

    VL - 378

    SP - 1408

    EP - 1418

    JO - New England Journal of Medicine

    JF - New England Journal of Medicine

    SN - 0028-4793

    IS - 15

    ER -

    Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. New England Journal of Medicine. 2018 Apr 12;378(15):1408-1418. https://doi.org/10.1056/NEJMoa1715546