Abstract 674P
Background
In recent years, NGHT initially approved for metastatic castration resistant PC (mCRPC) have also shown efficacy in non-metastatic CRPC (nmCRPC) and in hormone sensitive PC (HSPC). An earlier use and a longer duration of NGHT, added up to androgen deprivation therapy, requires evaluation of the impact on patient-reported outcomes (PROs), and particularly on CogF. Aim of this systematic review is to focus on the evidence about CogF in all randomized trials (RCTs) testing NGHT in patients (pts) with PC.
Methods
All RCTs testing abiraterone acetate (Abi), enzalutamide (Enz), apalutamide (Apa), darolutamide (Dar) were searched in Pubmed and major meetings. For each RCT, we assessed (i) availability of investigator-assessed cognitive impairment and disorders; (ii) availability of PRO-based evaluation of CogF.
Results
17 RCTs (17300 pts, 9793 assigned to NGHT) were included in the analysis (Table). Investigator-based evaluation of the incidence of cognitive impairment was available in 7 RCTs (41.2%): 1 mCRPC, 3 nmCRPC, 3 HSPC (Table). 17 / 17 RCTs (100%) included PROs collection, but PRO tools adopted allowed evaluation of CogF in 2 RCTs (11.8%). Among them, PRO-based CogF results were presented only in 1 RCT (5.9%) (Table): in ENZAMET, testing Enz in HSPC, mean changes were worse with Enz (p<0.0001), but deterioration-free survival favored Enz vs placebo (p=0.0003). Table: 674P
| Comparison | RCTs | Cog impairment (Investigator-assessed) | Cog function (PRO-based) | ||
| N | Toxicity (any grade) | N | Main results | ||
| Abi vs Ctrl | 5 | 1 | STAMPEDE: Cog imp. 6.4% vs 3.8% | 0 | - |
| Enz vs Ctrl | 7 | 3 | PROSPER: Cog / memory imp. 5% vs 2% ARCHES: Cog / memory imp. 4.5% vs 2.1% ENZAMET: Cog dist. 2.8% vs 0.5%; concentration imp. 5.3% vs 1.1%; memory imp. 14.6% vs 3.6%. | 1 | ENZAMET: mean changes worse for Enz (p<0.0001); deterioration-free survival better for Enz (3-yr 33% vs 21%, p=0.0003) |
| Apa vs Ctrl | 2 | 1 | SPARTAN: mental imp. 5.1% vs 3.0% | 0 | - |
| Dar vs Ctrl | 1 | 1 | ARAMIS: Cog disorders 0.4% vs 0.2%; memory imp. 0.5% vs 1.3% | 0 | - |
| Cabazitaxel vs Abi / Enz | 1 | 0 | - | 0 | - |
| Abi vs Enz | 1 | 1 | NCT02125357: Montreal <26 at week 12: 47% vs 54% | 0 | - |
| TOTAL | 17 | 7 (41.2%) | 1 (5.9%) |
Conclusions
Clinical development of NGHT has not included a systematic evaluation of CogF. Assessment by investigators is at risk of underreporting, but cognitive deterioration could be clinically relevant, at least in a proportion of pts. Commonly used PROs do not allow (FACT-P) or allow only partially (EORTC C30) CogF analysis. Furthermore, methodology of analysis can jeopardize interpretation of CogF results. Although direct comparisons are scanty, there could be differences between different NGTH.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Marandino: Travel/Accommodation/Expenses: Sanofi. C. Buttigliero: Honoraria (self), Advisory/Consultancy: Janssen. M. Di Maio: Research grant/Funding (institution): Tesaro GSK; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Takeda. All other authors have declared no conflicts of interest.