Skin Rash Following Administration of Apalutamide in Japanese Patients with Advanced Prostate Cancer: An Integrated Analysis of the Phase 3 SPARTAN and TITAN Studies and a Phase 1 Open-Label Study

Abstract Background: A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). Methods: This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (NCT01946204; patients with non‑metastatic castration-resistant PC [nmCRPC]) and TITAN (NCT02489318; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (NCT02162836; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio. Results: Data from 68 patients ( SPARTAN: n=34, TITAN: n=28, 56021927PCR1008: n=6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 hours) (AUC 0-24, ss ) at steady‑state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without. Conclusions: No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide‑related skin rash is easily managed, with appropriate treatment with or without dose adjustment.

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Skin Rash Following Administration of Apalutamide in Japanese Patients with Advanced Prostate Cancer: An Integrated Analysis of the Phase 3 SPARTAN and TITAN Studies and a Phase 1 Open-Label Study

10.21203/rs.3.rs-26754/v1 ◽

2020 ◽

Author(s):

Hiroji Uemura ◽

Yosuke Koroki ◽

Yuki Iwaki ◽

Keiichiro Imanaka ◽

Takeshi Kambara ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Skin Rash ◽

Phase 1 ◽

Japanese Patients ◽

Clinical Risk Factors ◽

Integrated Analysis ◽

Plasma Exposure ◽

Phase 3 ◽

Clinical Risk

Abstract Background A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC).Methods This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (NCT01946204; patients with nonmetastatic castration-resistant PC [nmCRPC]) and TITAN (NCT02489318; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (NCT02162836; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio.Results Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analysed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0–24 hours) (AUC0 − 24ss) at steadystate of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without.Conclusions No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamiderelated skin rash is easily managed, with appropriate treatment with or without dose adjustment.

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Skin Rash Following Administration of Apalutamide in Japanese Patients with Advanced Prostate Cancer: An Integrated Analysis of the Phase 3 SPARTAN and TITAN Studies and a Phase 1 Open-Label Study

10.21203/rs.3.rs-26754/v3 ◽

2020 ◽

Author(s):

Hiroji Uemura ◽

Yosuke Koroki ◽

Yuki Iwaki ◽

Keiichiro Imanaka ◽

Takeshi Kambara ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Skin Rash ◽

Phase 1 ◽

Japanese Patients ◽

Clinical Risk Factors ◽

Integrated Analysis ◽

Plasma Exposure ◽

Phase 3 ◽

Clinical Risk

Abstract Background: A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). Methods: This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (NCT01946204; patients with non‑metastatic castration-resistant PC [nmCRPC]) and TITAN (NCT02489318; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (NCT02162836; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio.Results: Data from 68 patients (SPARTAN: n=34, TITAN: n=28, 56021927PCR1008: n=6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 hours) (AUC0-24, ss) at steady‑state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without.Conclusions: No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide‑related skin rash is easily managed, with appropriate treatment with or without dose adjustment. Trial Registration: Retrospective pooled analysis of NCT01946204, NCT02489318, and NCT02162836

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Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study

BMC Urology ◽

10.1186/s12894-020-00689-0 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Hiroji Uemura ◽

Yosuke Koroki ◽

Yuki Iwaki ◽

Keiichiro Imanaka ◽

Takeshi Kambara ◽

...

Keyword(s):

Risk Factors ◽

Skin Rash ◽

Phase 1 ◽

Japanese Patients ◽

Clinical Risk Factors ◽

Integrated Analysis ◽

Plasma Exposure ◽

Phase 3 ◽

Clinical Risk ◽

Link Type

Abstract Background A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). Methods This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (NCT01946204; patients with non-metastatic castration-resistant PC [nmCRPC]) and TITAN (NCT02489318; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (NCT02162836; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio. Results Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36–1.81) and 1.0 month (IQR: 0.30–2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0–24 h) (AUC0–24, ss) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without. Conclusions No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment. Trial registration Retrospective pooled analysis of NCT01946204, NCT02489318, and NCT02162836.

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Correction to: Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study

BMC Urology ◽

10.1186/s12894-020-00739-7 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Hiroji Uemura ◽

Yosuke Koroki ◽

Yuki Iwaki ◽

Keiichiro Imanaka ◽

Takeshi Kambara ◽

...

Keyword(s):

Prostate Cancer ◽

Skin Rash ◽

Advanced Prostate Cancer ◽

Phase 1 ◽

Japanese Patients ◽

Integrated Analysis ◽

Open Label ◽

Phase 3 ◽

Open Label Study ◽

Label Study

An amendment to this paper has been published and can be accessed via the original article.

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OBESITY AND PROSTATE CANCER CLINICAL RISK FACTORS AT PRESENTATION: DATA FROM CaPSURE

The Journal of Urology ◽

10.1097/01.ju.0000152408.25738.23 ◽

2005 ◽

Vol 173 (3) ◽

pp. 732-736 ◽

Cited By ~ 39

Author(s):

CHRISTOPHER J. KANE ◽

WILLIAM W. BASSETT ◽

NATALIA SADETSKY ◽

STEFANIE SILVA ◽

KATRINE WALLACE ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Clinical Risk Factors ◽

Clinical Risk

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Clinical Risk Factors for Osteoporotic Fractures in Men With Non-Metastatic Prostate Cancer on Androgen Deprivation Therapy With or Without Anti-Osteoporosis Treatment

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.495 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A243-A244

Author(s):

Hajerah Sonnabend ◽

Vishnu Priya Pulipati ◽

Sanford Baim ◽

Todd Beck ◽

J Alan Simmons ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Cancer Therapy ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Clinical Risk Factors ◽

Mineral Density ◽

Steroid Use ◽

Clinical Risk ◽

Significant Difference

Abstract Introduction: Androgen deprivation therapy (ADT) decreases bone mineral density and increases osteoporotic fracture (OsteoFx) risk. Hypothesis: To assess OsteoFx clinical risk factors (CRF) most predictive of future OsteoFx among men with prostate cancer on ADT. Methods: 4370 electronic medical records were reviewed of adult men with prostate cancer on cancer therapy +/- anti-osteoporosis therapy (Anti-OsteoRx) from 2011–2019. Cancer therapy included ADT (anti-androgens, GnRH agonists & antagonists, orchiectomy) and supplemental cancer therapy (SupplRx) (prostatectomy, brachytherapy, radiation, immunotherapy, and chemotherapy). Anti-OsteoRx included bisphosphonates, denosumab, and parathyroid hormone analogs. Patients with other cancers within 5 years of initial visit, metastasis, and traumatic fractures were excluded. Retrospective analysis was done to determine baseline characteristics, type and duration of ADT, Anti-OsteoRx, SupplRx, and osteoporosis CRF. Results: 615 men on ADT +/- SupplRx +/- Anti-OsteoRx were included in the study. 10.08% had OsteoFx irrespective of SupplRx or Anti-OsteoRx. Comparing the OsteoFx group to the non-fracture group, the following CRF were found to be statistically significant (p <0.05): age at prostate cancer diagnosis (75.10 +/- 11.80 vs 71.59 +/- 9.80 y), diabetes mellitus (DM) (33.9 vs 19%), pre-existing comorbidities affecting bone (PreCo) (41.9 vs 24.8%), steroid use (11.3 vs 4.0%), and anti-convulsant and proton-pump inhibitor (med) use (45.2 vs 26.8%). 9.89% of 374 men on ADT only without (wo) Anti-OsteoRx fractured. Statistically significant CRF for OsteoFx were age (76.86 +/- 10.55 vs 73.02 +/- 10.06 y), DM (40.5 vs 19.6%), PreCo (45.9 vs. 26.4%), and med use (48.6 vs. 25.5%). In the following subgroups there were no statistically significant difference in CRF:•7.64% of 170 men on ADT + SupplRx wo Anti-OsteoRx •19.23% of 52 men on ADT only + Anti-OsteoRx •10.52% of 19 men on ADT + SupplRx + Anti-OsteoRx To increase statistical power, patients on ADT +/- SupplRx were assessed:•Among 71 men on ADT +/- SupplRx + Anti-OsteoRx, there were no statistically significant differences in CRF•Among the 544 men on ADT +/- SupplRx wo Anti-OsteoRx, significant CRF for OsteoFx were age (75.16 + 11.70 vs 71.37 + 9.85 y), DM (38 vs 19.4%), PreCo (38 vs 24.1%), steroid use (12 vs 3.8%), and med use (48 vs 24.3%) Discussion: Men with prostate cancer requiring ADT have a higher incidence of osteoporosis defined by DXA prior to initiating ADT compared to age-matched cohorts (Hussain et al). Our study revealed ADT with CRF is associated with OsteoFx irrespective of SupplRx or Anti-OsteoRx. Limitations include inability to evaluate efficacy of Anti-OsteoRx due to insufficient power. Conclusion: OsteoFx risk assessment utilizing CRF, FRAX, DXA with timely intervention may prevent OsteoFx in these high-risk patients.

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