Health-related quality of life (HRQoL) after progressive disease (PD) in SPARTAN: A phase III trial of apalutamide (APA) versus placebo (PBO) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC)
Bibliographic record
Abstract
Background: Compared with PBO, APA prolongs the median metastasis-free survival (MFS) by > 2 y (HR = 0.30; 95% CI, 0.24-0.36), and provids a 55% reduction in the risk of symptomatic progression (Sx PD) (HR = 0.45; 95% CI, 0.32-0.63) in patients (pts) with nmCRPC (SPARTAN study, Smith MR, et al. NEJM 2018), with no decline in HRQoL in either treatment group up to the time of developing distant metastases (Mets). Here, we report pt HRQoL following PD. Methods: 1207 pts (median age, both arms: 74 y) with nmCRPC were randomized 2:1 to APA (240 mg QD) or PBO. ADT was continued in all pts. HRQoL was assessed using the pt-reported outcome (PRO) questionnaire Functional Assessment of Cancer Therapy-Prostate (FACT-P). Following development of Mets, pts in the 2 arms received similar treatments, and PROs were collected at 4, 8, and 12 mo. Sx PD was defined as 1) development of a skeletal-related event; 2) initiation of new systemic anticancer treatment due to pain progression or worsening of disease-related symptoms; or 3) development of clinically significant symptoms due to loco-regional tumor progression requiring surgery or radiation. Descriptive statistics were performed for all FACT-P subscales. Results: Group mean PRO scores after PD were available from 341 pts and from 60 pts after Sx PD (Table). These PRO scores were similar for APA vs PBO up to 12 mo after PD. While APA delayed time to Sx PD, once Sx PD was reached there were similar numeric decreases from baseline across FACT-P subdomains up to 12 mo after Sx PD. Conclusions: Relative to PBO, pts treated with APA had a longer MFS, with no decline in HRQoL through the time of Mets, and similar HRQoL after Mets. Sx PD was delayed with APA vs PBO and was associated with a decline in HRQoL in both groups. Thus, HRQoL decline for pts treated with APA was delayed because of a longer time to Sx PD.Table: 804PPRO group mean scoresAPAPBOBaselineBefore MetsAfter MetsaIncludes pts with and without subsequent approved treatment for metastatic CRPC. SE, standard error.BaselineBefore MetsAfter MetsaIncludes pts with and without subsequent approved treatment for metastatic CRPC. SE, standard error.All pts, n797772157396384184Group mean (SE)FACT-P FACT-G117.2 (0.7) 84.1 (0.4)117.4 (0.7) 83.9 (0.5)112.5 (1.9) 80.7 (1.3)116.6 (1.0) 83.4 (0.7)116.6 (1.0) 83.2 (0.7)114.5 (1.6) 81.8 (1.1)BaselineBefore Sx PDAfter Sx PDaIncludes pts with and without subsequent approved treatment for metastatic CRPC. SE, standard error.BaselineBefore Sx PDAfter Sx PDaIncludes pts with and without subsequent approved treatment for metastatic CRPC. SE, standard error.Sx PD subgroup, n646430636330Group mean (SE)FACT-P FACT-G115.2 (2.5) 84.4 (1.9)117.0 (2.4) 84.2 (1.7)108.6 (3.7) 78.6 (2.9)117.8 (2.0) 85.2 (1.5)114.5 (2.2) 82.6 (1.7)105.6 (4.3) 75.3 (3.4)a Includes pts with and without subsequent approved treatment for metastatic CRPC. SE, standard error. Open table in a new tab Clinical trial identification: NCT01946204. Editorial acknowledgement: This study was funded by Janssen Research & Development. Writing assistance was provided by Ann Tighe, PhD, of PAREXEL, and was funded by Janssen Global Services, LLC. Legal entity responsible for the study: Janssen Research & Development. Funding: Janssen Research & Development. Disclosure: D. Cella: Consultant: AbbVie, Astellas, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Inc, Evidera, GlaxoSmithKline, Helsinn, Ipsen, Janssen Research & Development, Novartis; President: FACIT.org. F. Saad: Grants, Personal fees, Non-financial support: Janssen, Astellas, Sanofi, Bayer. B.A. Hadaschik: Grants: German Cancer Aid, German Research Foundation, Profound Medical; Grants Janssen, Uromed; Personal fees: Janssen, Astellas, Bayer, Uromed; Non-financial support: Janssen, Astellas, Bayer. J.N. Graff: Grants: Janssen, Sanofi, Astellas, Merck Bristol-Myers Squibb; Personal fees: Janssen, Sanofi, Astellas, Bayer, Dendreon. H. Uemura: Personal fees: Janssen, Astellas, Takeda, Sanofi, Bayer, and Astra-Zeneca. S. Oudard: Personal fees: Janssen, Sanofi, Astellas, Bayer, Merck. S. Hudgens: Consulting fees: Janssen. K. McQuarrie, M.K. Yu, A. Lopez-Gitlitz, B. Rooney: Employee: Janssen Research & Development; Stock owner: Johnson & Johnson. M. Morris: Consulting fees: Janssen. M.R. Smith: Grants: Janssen; Personal fees: Janssen, Astellas, Bayer. All other authors have declared no conflicts of interest.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".