Spartan Trial Information on Apalutam... - Advanced Prostate...

Advanced Prostate Cancer

20,785 members25,896 posts

Spartan Trial Information on Apalutamide. Great Results!

Moespy profile image
1 Reply

onclive.com/web-exclusives/...

Written by
Moespy profile image
Moespy
To view profiles and participate in discussions please or .
1 Reply
pjoshea13 profile image
pjoshea13

The new paper pertains only to QOL [1].

Basic results were published in February [2].

"... median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group ..."

(We don't yet know the effect on mortality.)

Note that "The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group ..." - not mentioned in the QOL article.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/302...

Lancet Oncol. 2018 Sep 10. pii: S1470-2045(18)30456-X. doi: 10.1016/S1470-2045(18)30456-X. [Epub ahead of print]

Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial.

Saad F1, Cella D2, Basch E3, Hadaschik BA4, Mainwaring PN5, Oudard S6, Graff JN7, McQuarrie K8, Li S9, Hudgens S10, Lawson J11, Lopez-Gitlitz A12, Yu MK12, Smith MR13, Small EJ14.

Author information

Abstract

BACKGROUND:

In the SPARTAN trial, addition of apalutamide to androgen deprivation therapy, as compared with placebo plus androgen deprivation therapy, significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer who were at high risk for development of metastases. We aimed to investigate the effects of apalutamide versus placebo added to androgen deprivation therapy on health-related quality of life (HRQOL).

METHODS:

SPARTAN is a multicentre, international, randomised, phase 3 trial. Participants were aged 18 years or older, with non-metastatic castration-resistant prostate cancer, a prostate-specific antigen doubling time of 10 months or less, and a prostate-specific antigen concentration of 2 ng/mL or more in serum. Patients were randomly assigned (2:1) to 240 mg oral apalutamide per day plus androgen deprivation therapy, or matched oral placebo plus androgen deprivation therapy, using an interactive voice randomisation system. Permuted block randomisation was used according to the three baseline stratification factors: prostate-specific antigen doubling time (>6 months vs ≤6 months), use of bone-sparing drugs (yes vs no), and presence of local-regional nodal disease (N0 vs N1). Each treatment cycle was 28 days. The primary endpoint was metastasis-free survival. The trial was unblinded in July, 2017. In this prespecified exploratory analysis we assessed HRQOL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires, which we collected at baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1-6, day 1 of every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter. This study is registered with ClinicalTrials.gov, number NCT01946204.

FINDINGS:

Between Oct 14, 2013, and Dec 15, 2016, we randomly assigned 1207 patients to receive apalutamide (n=806) or placebo (n=401). The clinical cutoff date, as for the primary analysis, was May 19, 2017. Median follow-up for overall survival was 20·3 months (IQR 14·8-26·6). FACT-P total and subscale scores were associated with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group; there were similar results for EQ-5D-3L. At baseline, the mean for FACT-P total score in both the apalutamide and placebo groups were consistent with the FACT-P general population norm for US adult men. Group mean patient-reported outcome scores over time show that HRQOL was maintained from baseline after initiation of apalutamide treatment and was similar over time among patients receiving apalutamide versus placebo. Least-squares mean change from baseline shows that HRQOL deterioration was more apparent in the placebo group.

INTERPRETATION:

In asymptomatic men with high-risk non-metastatic castration-resistant prostate cancer, HRQOL was maintained after initiation of apalutamide treatment. Considered with findings from SPARTAN, patients who received apalutamide had longer metastasis-free survival and longer time to symptomatic progression than did those who received placebo, while preserving HRQOL.

FUNDING:

Janssen Research & Development.

Copyright © 2018 Elsevier Ltd. All rights reserved.

PMID: 30213449 DOI: 10.1016/S1470-2045(18)30456-X

...

[2] ncbi.nlm.nih.gov/pubmed/294...

N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8.

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.

Smith MR1, Saad F1, Chowdhury S1, Oudard S1, Hadaschik BA1, Graff JN1, Olmos D1, Mainwaring PN1, Lee JY1, Uemura H1, Lopez-Gitlitz A1, Trudel GC1, Espina BM1, Shu Y1, Park YC1, Rackoff WR1, Yu MK1, Small EJ1; SPARTAN Investigators.

Collaborators (451)

Author information

Abstract

BACKGROUND:

Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.

METHODS:

We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.

RESULTS:

A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).

CONCLUSIONS:

Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204 .).

Comment in

Apalutamide and Metastasis-free Survival in Prostate Cancer. [N Engl J Med. 2018]

PMID: 29420164 DOI: 10.1056/NEJMoa1715546

[Indexed for MEDLINE]

You may also like...

Apalutamide - SPARTAN versus Enzalutamide - PROSPER.

os=1&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%202018-02-06&utm_term=Daily

SPARTAN (Apalutamide)

The Apalutamide study presented in SF recently was published in the NEJM yesterday [1]. The...

Good results with Apalutamide

I have been on apalutamide for 14 months and my PSA has gone from 4.5 down to 0.14. I have had the...

Dutasteride and Apalutamide

Avodart with Apalutamide to extend castrate sensitivity? I have been on Lupron/Apalutamide for >2...

Apalutamide compared to the other Lutamides

Apalutamide sounds like a great choice for those that are Metastatic and still Hormone Sensitive....