Safety and antitumor activity of apalutamide (ARN-509) in metastatic castration-resistant prostate cancer with and without prior abiraterone acetate and prednisone

Dana E. Rathkopf, Emmanuel Antonarakis, Neal D. Shore, Ronald F. Tutrone, Joshi J. Alumkal, Charles J. Ryan, Mansoor Saleh, Ralph J. Hauke, Rajesh Bandekar, Edna Chow Maneval, Carla J. De Boer, Margaret K. Yu, Howard I. Scher

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Experimental Design: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day. Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and time on treatment. Results: Forty-six patients enrolled in the AAP-naïve (n ¼ 25) and post-AAP (n ¼ 21) cohorts. The 12-week PSA response rate was 88% (22/25) and 22% (4/18), median time to PSA progression was 18.2 months [95% confidence interval (CI), 8.3 months–not reached) and 3.7 months (95% CI, 2.8–5.6 months), and median time on treatment 21 months (range, 2.6–37.5) and 4.9 months (range, 1.3–23.2), for the AAP-naïve and post-AAP cohorts, respectively. Eighty percent (95% CI, 59–93) and 64% (95% CI, 43–82) of AAP-naïve and 43% (95% CI, 22–66) and 10% (95% CI, 1–30) of post-AAP patients remained on treatment for 6þ and 12þ months, respectively. Common treatment-emergent adverse events in both cohorts were grade 1 or 2 fatigue, diarrhea, nausea, and abdominal pain. Conclusions: Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80% of AAP-naïve and 43% of post-AAP patients, remaining on treatment for 6 months or longer.

Original languageEnglish (US)
Pages (from-to)3544-3551
Number of pages8
JournalClinical Cancer Research
Volume23
Issue number14
DOIs
StatePublished - Jul 15 2017

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Castration
Prednisone
Prostatic Neoplasms
Safety
Prostate-Specific Antigen
Confidence Intervals
Abiraterone Acetate
ARN-509
Therapeutics
Nausea
Abdominal Pain
Fatigue
Diarrhea
Research Design

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Safety and antitumor activity of apalutamide (ARN-509) in metastatic castration-resistant prostate cancer with and without prior abiraterone acetate and prednisone. / Rathkopf, Dana E.; Antonarakis, Emmanuel; Shore, Neal D.; Tutrone, Ronald F.; Alumkal, Joshi J.; Ryan, Charles J.; Saleh, Mansoor; Hauke, Ralph J.; Bandekar, Rajesh; Maneval, Edna Chow; De Boer, Carla J.; Yu, Margaret K.; Scher, Howard I.

In: Clinical Cancer Research, Vol. 23, No. 14, 15.07.2017, p. 3544-3551.

Research output: Contribution to journalArticle

Rathkopf, DE, Antonarakis, E, Shore, ND, Tutrone, RF, Alumkal, JJ, Ryan, CJ, Saleh, M, Hauke, RJ, Bandekar, R, Maneval, EC, De Boer, CJ, Yu, MK & Scher, HI 2017, 'Safety and antitumor activity of apalutamide (ARN-509) in metastatic castration-resistant prostate cancer with and without prior abiraterone acetate and prednisone', Clinical Cancer Research, vol. 23, no. 14, pp. 3544-3551. https://doi.org/10.1158/1078-0432.CCR-16-2509
Rathkopf, Dana E. ; Antonarakis, Emmanuel ; Shore, Neal D. ; Tutrone, Ronald F. ; Alumkal, Joshi J. ; Ryan, Charles J. ; Saleh, Mansoor ; Hauke, Ralph J. ; Bandekar, Rajesh ; Maneval, Edna Chow ; De Boer, Carla J. ; Yu, Margaret K. ; Scher, Howard I. / Safety and antitumor activity of apalutamide (ARN-509) in metastatic castration-resistant prostate cancer with and without prior abiraterone acetate and prednisone. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 14. pp. 3544-3551.
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abstract = "Purpose: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Experimental Design: Two cohorts were studied: AAP-na{\"i}ve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day. Primary endpoint was ≥50{\%} decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and time on treatment. Results: Forty-six patients enrolled in the AAP-na{\"i}ve (n ¼ 25) and post-AAP (n ¼ 21) cohorts. The 12-week PSA response rate was 88{\%} (22/25) and 22{\%} (4/18), median time to PSA progression was 18.2 months [95{\%} confidence interval (CI), 8.3 months–not reached) and 3.7 months (95{\%} CI, 2.8–5.6 months), and median time on treatment 21 months (range, 2.6–37.5) and 4.9 months (range, 1.3–23.2), for the AAP-na{\"i}ve and post-AAP cohorts, respectively. Eighty percent (95{\%} CI, 59–93) and 64{\%} (95{\%} CI, 43–82) of AAP-na{\"i}ve and 43{\%} (95{\%} CI, 22–66) and 10{\%} (95{\%} CI, 1–30) of post-AAP patients remained on treatment for 6{\th} and 12{\th} months, respectively. Common treatment-emergent adverse events in both cohorts were grade 1 or 2 fatigue, diarrhea, nausea, and abdominal pain. Conclusions: Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80{\%} of AAP-na{\"i}ve and 43{\%} of post-AAP patients, remaining on treatment for 6 months or longer.",
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T1 - Safety and antitumor activity of apalutamide (ARN-509) in metastatic castration-resistant prostate cancer with and without prior abiraterone acetate and prednisone

AU - Rathkopf, Dana E.

AU - Antonarakis, Emmanuel

AU - Shore, Neal D.

AU - Tutrone, Ronald F.

AU - Alumkal, Joshi J.

AU - Ryan, Charles J.

AU - Saleh, Mansoor

AU - Hauke, Ralph J.

AU - Bandekar, Rajesh

AU - Maneval, Edna Chow

AU - De Boer, Carla J.

AU - Yu, Margaret K.

AU - Scher, Howard I.

PY - 2017/7/15

Y1 - 2017/7/15

N2 - Purpose: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Experimental Design: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day. Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and time on treatment. Results: Forty-six patients enrolled in the AAP-naïve (n ¼ 25) and post-AAP (n ¼ 21) cohorts. The 12-week PSA response rate was 88% (22/25) and 22% (4/18), median time to PSA progression was 18.2 months [95% confidence interval (CI), 8.3 months–not reached) and 3.7 months (95% CI, 2.8–5.6 months), and median time on treatment 21 months (range, 2.6–37.5) and 4.9 months (range, 1.3–23.2), for the AAP-naïve and post-AAP cohorts, respectively. Eighty percent (95% CI, 59–93) and 64% (95% CI, 43–82) of AAP-naïve and 43% (95% CI, 22–66) and 10% (95% CI, 1–30) of post-AAP patients remained on treatment for 6þ and 12þ months, respectively. Common treatment-emergent adverse events in both cohorts were grade 1 or 2 fatigue, diarrhea, nausea, and abdominal pain. Conclusions: Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80% of AAP-naïve and 43% of post-AAP patients, remaining on treatment for 6 months or longer.

AB - Purpose: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Experimental Design: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day. Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and time on treatment. Results: Forty-six patients enrolled in the AAP-naïve (n ¼ 25) and post-AAP (n ¼ 21) cohorts. The 12-week PSA response rate was 88% (22/25) and 22% (4/18), median time to PSA progression was 18.2 months [95% confidence interval (CI), 8.3 months–not reached) and 3.7 months (95% CI, 2.8–5.6 months), and median time on treatment 21 months (range, 2.6–37.5) and 4.9 months (range, 1.3–23.2), for the AAP-naïve and post-AAP cohorts, respectively. Eighty percent (95% CI, 59–93) and 64% (95% CI, 43–82) of AAP-naïve and 43% (95% CI, 22–66) and 10% (95% CI, 1–30) of post-AAP patients remained on treatment for 6þ and 12þ months, respectively. Common treatment-emergent adverse events in both cohorts were grade 1 or 2 fatigue, diarrhea, nausea, and abdominal pain. Conclusions: Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80% of AAP-naïve and 43% of post-AAP patients, remaining on treatment for 6 months or longer.

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