1632P - Impact of androgen pathway inhibitors on cognitive function in elderly patients with metastatic prostate cancer: Results from the COG-PRO trial

Background

Androgen deprivation therapy (ADT) for metastatic prostate cancer (mPC) adversely impacts cognitive performance (objective cognition, OC) and increases perceived cognitive impairment (subjective cognition, SC). Androgen pathway inhibitors (ARPI) are commonly used in mPC, however few data are available on their impact on cognition in elderly patients (pts).

Methods

The COG-PRO trial was designed to assess cognition in castration-resistant mPC (mCRPC) pts aged ≥70 before initiation of ARPI (enzalutamide or abiraterone acetate plus prednisone) in addition to ADT, and after 3, 6, and 12 months, compared with pts receiving ADT alone, and healthy controls (HC). SC was examined with the Perceived cognitive impairment (PCI) and abilities (PCA) subscales of the FACT-COG questionnaire, and OC with cognitive tests assessing 6 objective domains (processing speed / attention, working memory, verbal memory, visual memory, visuospatial abilities, and executive functions). Overall OC impairment at baseline and OC declines during follow-up were estimated using ICCTF guidelines and reliable change index, respectively. Adjusted scores were then analyzed using linear models for objective domains separately and for SC.

Results

The analysis was conducted in 74 ADT+ARPI pts, 19 ADT pts, and 30 HC (aged 78, 74, and 75, respectively). At baseline, 51% of ADT+ARPI pts had overall OC impairment, vs. 26% of ADT pts (p=0.072) and 10% of HC (p<0.001). During follow-up, incidence of overall OC decline in ADT+ARPI pts ranged from 2% to 6%. Adjusted scores showed lower performance in mPC pts compared to HC throughout follow-up in processing speed/attention, working memory, verbal memory and executive function (p≤0.027) and for SC (PCI: p≤0.005). Adjusted scores also showed lower performance for ADT+ARPI pts compared to ADT pts for processing speed/attention at each visit (p≤0.010). ADT+ARPI pts also reported poorer SC in the first 6 months of treatment compared to ADT (PCA: p≤0.033).

Conclusions

Cognitive impairment is frequent in elderly mPC patients treated with ADT. ARPI appear to enhance the adverse cognitive effects ADT on OC and SC, and this should be considered in elderly pts candidates for these treatments.

Clinical trial identification

NCT02907372.

Editorial acknowledgement

Legal entity responsible for the study

François Baclesse Center, Caen, France.

Funding

Astellas Pharma.

Disclosure

G. Baciarello: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: Novartis, Bayer, Astellas; Financial Interests, Institutional, Steering Committee Member: Bayer; Non-Financial Interests, Principal Investigator: Roche, Eli Lilly, MSD; Non-Financial Interests, Personal, Other, Meeting registration: Ipsen; Non-Financial Interests, Personal, Other, Travel Grant and meeting registration: Bayer; Non-Financial Interests, Member: ASCO, Meet-Uro. E. Meyer: Financial Interests, Personal, Invited Speaker: Ipsen, Astellas, Recordati. R. Ratta: Financial Interests, Personal, Invited Speaker: Ipsen, Astellas; Financial Interests, Personal, Advisory Board: Pfizer, Merck, Bristol Meyer Squibb, AstraZeneca, Janssen, Novartis. E. Guerdoux: Financial Interests, Personal, Invited Speaker, Speech about return to work after a cancer: CanceroConsult; Non-Financial Interests, Principal Investigator, Clinical trials on cognitive complaints in cancer, on psychological impacts of cancer or anti-cancer treatment: Montpellier Cancer Institute, Supportive care Department. A. Darlix: Financial Interests, Personal, Advisory Board: Servier, Novocure. M. Boone: Financial Interests, Personal, Advisory Board, Expert Board 18/04/2024: Servier; Financial Interests, Personal, Invited Speaker: Novocure. B. Clarisse: Financial Interests, Institutional, Other, Institutional financial support and drug supply for TALASUR trial conduction: Pfizer; Financial Interests, Institutional, Other, Institutional financial support for the CogPRO trial: Astellas; Non-Financial Interests, Institutional, Product Samples, drug supply for patients enrolled in the TALASUR trial: Pfizer. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Personal, Advisory Board, February 2022: Arvinas; Financial Interests, Personal, Advisory Board, April 2022: Macrogenics; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the CAPITELLO 281 phase 3 trial: AstraZeneca; Non-Financial Interests, Principal Investigator, Chair of the TALAPRO-2 and TALAPRO-3 phase 3 trials: Pfizer; Non-Financial Interests, Principal Investigator, Chair of the RADIANT phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the TRITON-3 phase 3 trial: Clovis. F. Joly Lobbedez: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, MSD, Janssen, Ipsen, Bayer, Astellas, Eisai, Seagen, Novocure, Pfizer; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, MSD, Janssen, Ipsen, Amgen, Novartis/3A, Eisai, Amgen, Eisai; Financial Interests, Institutional, Invited Speaker: Viatris; Financial Interests, Institutional, Coordinating PI: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS, Astellas; Financial Interests, Institutional, Funding: Janssen; Non-Financial Interests, Member: GCIG; Other, travel and congress: MSD, Ipsen, Chugai; Other, travel: GSK, Eisai. All other authors have declared no conflicts of interest.