Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer
Purpose. This randomized phase 2 study sought to assess the treatment effect of a finite duration of apalutamide with and without androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BCR PC). Materials and Methods. Patients with BCR PC after primary definitive therapy and p...
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Wiley
2022-01-01
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| Series: | Prostate Cancer |
| Online Access: | http://dx.doi.org/10.1155/2022/5454727 |
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| author | Rahul Aggarwal Joshi J. Alumkal Russell Z. Szmulewitz Celestia S. Higano Alan H. Bryce Angela Lopez-Gitlitz Sharon A. McCarthy Branko Miladinovic Kelly McQuarrie Shibu Thomas Ke Zhang Eric J. Small |
| author_facet | Rahul Aggarwal Joshi J. Alumkal Russell Z. Szmulewitz Celestia S. Higano Alan H. Bryce Angela Lopez-Gitlitz Sharon A. McCarthy Branko Miladinovic Kelly McQuarrie Shibu Thomas Ke Zhang Eric J. Small |
| author_sort | Rahul Aggarwal |
| collection | DOAJ |
| description | Purpose. This randomized phase 2 study sought to assess the treatment effect of a finite duration of apalutamide with and without androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BCR PC). Materials and Methods. Patients with BCR PC after primary definitive therapy and prostate-specific antigen (PSA) doubling time ≤12 months were randomized to open-label apalutamide (240 mg/d) alone, apalutamide plus ADT, or ADT alone (1 : 1:1 ratio) for 12 months followed by a 12-month observation period (NCT01790126). Mean changes from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) at 12 months (primary endpoint) and other prespecified assessments of health-related quality of life (HRQoL), PSA nadir, time to PSA progression, time to testosterone recovery, recovered testosterone >150 ng/dL without PSA progression at 24 months, and molecular markers were evaluated. Results. In 90 enrolled patients (apalutamide plus ADT (n = 31), apalutamide (n = 29), ADT (n = 30)), FACT-P at 12 months was not significantly different between apalutamide, ADT and apalutamide, and ADT groups. Addition of apalutamide to ADT prolonged time to PSA progression but this change did not reach statistical significance (hazard ratio (HR): 0.56, 95% confidence interval (CI): 0.23–1.36, P=0.196); time to testosterone recovery was similar in the ADT-containing groups. In apalutamide plus ADT, apalutamide, and ADT groups, 37.9%, 37.0%, and 19.2% of patients, respectively, had testosterone >150 ng/dL at 24 months without confirmed PSA progression. Of the few biomarkers expressed in blood, EPHA3 was significantly associated with shorter time to PSA progression (P=0.02) in the overall population. Conclusions. HRQoL was similar in patients treated with apalutamide alone, ADT alone, or their combination, although apalutamide plus ADT did not demonstrate statistically significant noninferiority in change from baseline in overall HRQoL. The aggregated efficacy and safety outcomes support further evaluation of apalutamide plus ADT in BCR PC. |
| format | Article |
| id | doaj-art-ca0c2ba8c68e4aca981effd45231b1a2 |
| institution | Kabale University |
| issn | 2090-312X |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
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| series | Prostate Cancer |
| spelling | doaj-art-ca0c2ba8c68e4aca981effd45231b1a22025-02-03T05:57:29ZengWileyProstate Cancer2090-312X2022-01-01202210.1155/2022/5454727Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate CancerRahul Aggarwal0Joshi J. Alumkal1Russell Z. Szmulewitz2Celestia S. Higano3Alan H. Bryce4Angela Lopez-Gitlitz5Sharon A. McCarthy6Branko Miladinovic7Kelly McQuarrie8Shibu Thomas9Ke Zhang10Eric J. Small11Helen Diller Family Comprehensive Cancer CenterKnight Cancer InstituteUniversity of ChicagoUniversity of WashingtonMayo Clinic ArizonaJanssen Research & DevelopmentJanssen Research & DevelopmentJanssen Research & DevelopmentMerckJanssen Research & DevelopmentJanssen Research & DevelopmentHelen Diller Family Comprehensive Cancer CenterPurpose. This randomized phase 2 study sought to assess the treatment effect of a finite duration of apalutamide with and without androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BCR PC). Materials and Methods. Patients with BCR PC after primary definitive therapy and prostate-specific antigen (PSA) doubling time ≤12 months were randomized to open-label apalutamide (240 mg/d) alone, apalutamide plus ADT, or ADT alone (1 : 1:1 ratio) for 12 months followed by a 12-month observation period (NCT01790126). Mean changes from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) at 12 months (primary endpoint) and other prespecified assessments of health-related quality of life (HRQoL), PSA nadir, time to PSA progression, time to testosterone recovery, recovered testosterone >150 ng/dL without PSA progression at 24 months, and molecular markers were evaluated. Results. In 90 enrolled patients (apalutamide plus ADT (n = 31), apalutamide (n = 29), ADT (n = 30)), FACT-P at 12 months was not significantly different between apalutamide, ADT and apalutamide, and ADT groups. Addition of apalutamide to ADT prolonged time to PSA progression but this change did not reach statistical significance (hazard ratio (HR): 0.56, 95% confidence interval (CI): 0.23–1.36, P=0.196); time to testosterone recovery was similar in the ADT-containing groups. In apalutamide plus ADT, apalutamide, and ADT groups, 37.9%, 37.0%, and 19.2% of patients, respectively, had testosterone >150 ng/dL at 24 months without confirmed PSA progression. Of the few biomarkers expressed in blood, EPHA3 was significantly associated with shorter time to PSA progression (P=0.02) in the overall population. Conclusions. HRQoL was similar in patients treated with apalutamide alone, ADT alone, or their combination, although apalutamide plus ADT did not demonstrate statistically significant noninferiority in change from baseline in overall HRQoL. The aggregated efficacy and safety outcomes support further evaluation of apalutamide plus ADT in BCR PC.http://dx.doi.org/10.1155/2022/5454727 |
| spellingShingle | Rahul Aggarwal Joshi J. Alumkal Russell Z. Szmulewitz Celestia S. Higano Alan H. Bryce Angela Lopez-Gitlitz Sharon A. McCarthy Branko Miladinovic Kelly McQuarrie Shibu Thomas Ke Zhang Eric J. Small Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer Prostate Cancer |
| title | Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer |
| title_full | Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer |
| title_fullStr | Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer |
| title_full_unstemmed | Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer |
| title_short | Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer |
| title_sort | randomized open label phase 2 study of apalutamide plus androgen deprivation therapy versus apalutamide monotherapy versus androgen deprivation monotherapy in patients with biochemically recurrent prostate cancer |
| url | http://dx.doi.org/10.1155/2022/5454727 |
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