trialsTrialPositive

PROSPER

PROSPER showed that enzalutamide delayed the appearance of metastases by about two years, and later helped men live longer, when given at the point where prostate cancer is rising on hormone therapy but has not yet spread on scans.

PROSPER randomised 1401 men with castration-resistant prostate cancer, no metastases on conventional imaging and a PSA doubling time of ten months or less two to one to enzalutamide or placebo alongside androgen deprivation. The primary endpoint was metastasis-free survival.

Enzalutamide lengthened metastasis-free survival substantially and delayed the time to PSA progression and to further antineoplastic therapy; with longer follow-up overall survival was also improved. Fatigue, hypertension and falls were the main added toxicities. It was approved for this indication in July 2018 and, with SPARTAN (apalutamide) and ARAMIS (darolutamide), defined androgen receptor pathway inhibition as the standard for high-risk non-metastatic castration-resistant disease, a group that PSMA PET imaging has since shrunk.

Setting

Non-metastatic castration-resistant prostate cancer with a PSA doubling time of ten months or less: enzalutamide against placebo, both with continued androgen deprivation

Phase

Phase 3

Sponsor

Pfizer (Medivation) and Astellas

Registry

NCT02003924

Headline result

Enzalutamide lengthened metastasis-free survival and, with longer follow-up, overall survival compared with placebo; approved in July 2018.

Reported

2018

Enrolled

1,401 enrolled

Outcomes

4top

In plain words

What these results mean for people, not percentages

1,401 enrolled

Metastasis-free survivalprimarysurrogate endpoint

Median 36.6 vs 14.7 months with Enzalutamide compared with Placebo; about 21.9 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 71 percent lower chance of the event at any given time (hazard ratio 0.29, likely range 0.24 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 PSA progressionother endpoint

Median 37.2 vs 3.9 months with Enzalutamide compared with Placebo; about 33.3 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 93 percent lower chance of the event at any given time (hazard ratio 0.07).

The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Time to first subsequent antineoplastic therapyother endpoint

Median 39.6 vs 17.7 months with Enzalutamide compared with Placebo; about 21.9 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 79 percent lower chance of the event at any given time (hazard ratio 0.21).

The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Grade 3 or higher adverse eventsother endpoint

31 vs 23 out of 100 reached this endpoint with Enzalutamide compared with Placebo; 8 more per 100.
On this measure the first group did worse, not better.

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: Non-metastatic castration-resistant prostate cancer with a PSA doubling time of ten months or less: enzalutamide against placebo, both with continued androgen deprivation. 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.

1,401 enrolled.

Metastasis-free survivalprimary

HR 0.29 (0.24 to 0.35) · p <0.001

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Source

Time to PSA progression

HR 0.07 · p <0.001

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Source

Time to first subsequent antineoplastic therapy

HR 0.21 · p <0.001

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Source

Grade 3 or higher adverse events

Enzalutamide31 of 100

Placebo23 of 100

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Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Metastasis-free survivalprimary	Enzalutamide	933	36.6 months	0.29 (0.24 to 0.35)	<0.001	link
Metastasis-free survivalprimary	Placebo	468	14.7 months	0.29 (0.24 to 0.35)	<0.001	link
Time to PSA progression	Enzalutamide	933	37.2 months	0.07	<0.001	link
Time to PSA progression	Placebo	468	3.9 months	0.07	<0.001	link
Time to first subsequent antineoplastic therapy	Enzalutamide	933	39.6 months	0.21	<0.001	link
Time to first subsequent antineoplastic therapy	Placebo	468	17.7 months	0.21	<0.001	link
Grade 3 or higher adverse events	Enzalutamide	-	31%	-	-	link
Grade 3 or higher adverse events	Placebo	-	23%	-	-	link