A Study of Apalutamide (ARN-509) in… · NCT01946204

A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer is a phase 3 interventional study registered as NCT01946204 by Aragon Pharmaceuticals, Inc., with 1207 participants enrolled, started 2013-10-14 and due to reach its primary completion in 2017-05-19. Interventions recorded: Apalutamide and Placebo. Results have been posted on the registry.

Setting

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study of ARN-509 in Men With Non-Metastatic (M0) Castration-Resistant Prostate Cancer

Phase

Phase 3

Sponsor

Aragon Pharmaceuticals, Inc.

Registry

NCT01946204

Headline result

Median metastasis-free survival 40.5 months with apalutamide added to androgen deprivation against 16.2 months with placebo (hazard ratio 0.28, 95 percent confidence interval 0.23 to 0.35, p<0.001); rash 23.8 against 5.5 percent and fracture 11.7 against 6.5 percent.

Started

2013-10-14

Reported

2018

Enrolled

1,207 enrolled

Replication

PROSPER with enzalutamide and ARAMIS with darolutamide found metastasis-free survival benefits of the same size in the same setting.

Outcomes

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In plain words

What these results mean for people, not percentages

1,207 enrolled

Metastasis-free survival (median)primarysurrogate endpoint

Median 40.5 vs 16.2 months with Apalutamide with androgen deprivation compared with Placebo with androgen deprivation; about 24.3 months longer for half the group.
A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
Put another way, the treated group had about 72 percent lower chance of the event at any given time (hazard ratio 0.28, likely range 0.23 to 0.35).

This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.

Time to symptomatic progressionother endpoint

The treated group had about 55 percent lower chance of the event at any given time (hazard ratio 0.45).
The absolute difference, how many more people out of 100 were helped, is not reported here.

This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Fracture, any gradeother endpoint

11.7 vs 6.5 out of 100 reached this endpoint with Apalutamide with androgen deprivation compared with Placebo with androgen deprivation; 5.2 more per 100.
Roughly one extra person helped for every 19 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Caveats

These results apply to the people the trial enrolled: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study of ARN-509 in Men With Non-Metastatic (M0) Castration-Resistant Prostate Cancer. People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

1,207 enrolled.

Metastasis-free survival (median)primary

HR 0.28 (0.23 to 0.35) · p <0.001

Download

Source

Time to symptomatic progression

HR 0.45 (0.32 to 0.63) · p <0.001

Numbers not yet public.

Source

Fracture, any grade

Apalutamide with androgen deprivation11.7 of 100

n = 806

Placebo with androgen deprivation6.5 of 100

n = 401

Download

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Metastasis-free survival (median)primary	Apalutamide with androgen deprivation	806	40.5 months	0.28 (0.23 to 0.35)	<0.001	link
Metastasis-free survival (median)primary	Placebo with androgen deprivation	401	16.2 months	0.28 (0.23 to 0.35)	<0.001	link
Time to symptomatic progression	Apalutamide with androgen deprivation	806	-	0.45 (0.32 to 0.63)	<0.001	link
Time to symptomatic progression	Placebo with androgen deprivation	401	-	0.45 (0.32 to 0.63)	<0.001	link
Fracture, any grade	Apalutamide with androgen deprivation	806	11.7%	-	-	link
Fracture, any grade	Placebo with androgen deprivation	401	6.5%	-	-	link

Replication

PROSPER with enzalutamide and ARAMIS with darolutamide found metastasis-free survival benefits of the same size in the same setting.

Notes

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SPARTAN randomised 1,207 men with non-metastatic castration-resistant prostate cancer and a PSA doubling time of 10 months or less 2:1 to apalutamide 240 mg daily or placebo, all continuing androgen deprivation. The primary analysis was performed after 378 events. Adverse events leading to discontinuation occurred in 10.6 percent on apalutamide and 7.0 percent on placebo; rash occurred in 23.8 against 5.5 percent and hypothyroidism in 8.1 against 2.0 percent (New England Journal of Medicine 2018).
In England NICE TA740 recommends apalutamide with androgen deprivation for hormone-relapsed non-metastatic prostate cancer at high risk of metastasising, defining high risk as a PSA that has doubled in 10 months or less on continuous androgen deprivation. NICE TA660 recommends darolutamide with androgen deprivation for the same population. NICE TA580 does not recommend enzalutamide there: the committee accepted that it extends the time until the cancer spreads, found no evidence that it extends life, and judged the cost-effectiveness estimates too uncertain and outside the usual range.
This disease state is partly an artefact of imaging. Men classified as non-metastatic on CT and bone scan, which is how SPARTAN, PROSPER and ARAMIS staged them, are frequently found to have metastases on PSMA PET.

Key papers

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rctNew England Journal of Medicine 2018changed practice986 citations

SPARTAN: apalutamide for non-metastatic castration-resistant prostate cancer

Apalutamide, enzalutamide or darolutamide are standard for high-risk non-metastatic castration-resistant prostate cancer, a setting largely defined by conventional imaging.

Connected

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Trial
A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer
Shares Apalutamide, Androgen deprivation & AR pathway inhibitors, Johnson & Johnson, Prostate cancer and the tag pipeline.
Trial
An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS
Shares Apalutamide, Androgen deprivation & AR pathway inhibitors, Johnson & Johnson, Prostate cancer and the tag pipeline.
Trial
A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
Shares Apalutamide, Androgen deprivation & AR pathway inhibitors, Johnson & Johnson, Prostate cancer and the tag pipeline.
Trial
A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma
Shares Apalutamide, Androgen deprivation & AR pathway inhibitors, Johnson & Johnson and the tag pipeline.
Trial
An Efficacy and Safety Study of Apalutamide (JNJ-56021927) in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Participants With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)
Shares Apalutamide, Androgen deprivation & AR pathway inhibitors, Johnson & Johnson, Prostate cancer and the tag pipeline.
Trial
A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-MutatedProstatic Neoplasms (mCSPC)
Shares Androgen deprivation & AR pathway inhibitors, Johnson & Johnson, Prostate cancer and the tag pipeline.
Trial
Conventional Androgen Deprivation Therapy (ADT) With or Without Abiraterone Acetate + Prednisone and Apalutamide Following a Detectable PSA After Radiation and ADT
Shares Apalutamide, Prostate cancer and the tag pipeline.
Trial
Study of HLD-0915 (JNJ-101556143) in Patients With Metastatic Prostate Cancer
Shares Johnson & Johnson, Prostate cancer and the tag pipeline.

cancers

Non-metastatic castration-resistant prostate cancer Prostate cancer

technologies

Androgen deprivation & AR pathway inhibitors

drugs

ApprovedSmall-molecule AR antagonist

Apalutamide · Erleada

A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer

Outcomes

Notes

Key papers

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A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer

Overview

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A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer

Overview

Outcomes

Notes

Key papers

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