1810P - Association of health-related quality of life with efficacy outcomes in the VISION study of patients with metastatic castration-resistant prostate cancer

Background

This post hoc analysis of the phase 3 VISION study of [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) plus standard of care (SoC) vs SoC alone in adults with progressive, prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC), assessed associations of PSA decline, radiographic progression-free survival (rPFS) and overall survival (OS) with time to worsening (TTW) of health-related quality of life (HRQoL).

Methods

Associations of PSA decline with TTW of HRQoL (n = 385) were assessed in the ¹⁷⁷Lu-PSMA-617 arm. Patients were grouped by PSA decline (unconfirmed) overall or up to 12 weeks of treatment: no decline, ≤ 50%, > 50 to ≤ 90% and > 90%. Worsening of HRQoL was defined as a decrease of ≥ 10 (total) or ≥ 3 (subdomain) points in FACT-P, an increase of ≥ 2 points in BPI-SF or any decrease in EQ-5D-5L. Associations of rPFS or OS with TTW of HRQoL were carried out in the full analysis set (FAS; N = 831) using three Spearman’s rank methods (restricted, highest rank, iterative multiple imputation), with and without imputation for missing OS and rPFS data.

Results

In the ¹⁷⁷Lu-PSMA-617 arm, greater PSA decline overall and up to 12 weeks of treatment was associated with longer median TTW in FACT-P total and subdomain scores (Table). Correlations of rPFS and OS with and without imputation with TTW of HRQoL were positive and significantly different to zero in both arms, but mainly weak/moderate. In the total FAS without imputation, rPFS correlations were 0.27–0.51 (FACT-P total), 0.19–0.34 (EQ-5D-5L) and 0.26–0.47 (BPI-SF severity); OS correlations were 0.41–0.55 (FACT-P total), 0.13–0.31 (EQ-5D-5L) and 0.20–0.55 (BPI-SF severity). Table: 1810P

HRQoL outcomes by magnitude of PSA decline

^aKaplan–Meier estimates; ^b177Lu-PSMA-617 + SoC group.

Conclusions

Greater PSA decline and increased rPFS and OS were associated with longer TTW of HRQoL. Ongoing analyses will assess associations of other HRQoL measures with PSA decline and overall response rate.

Clinical trial identification

EudraCT 2018-000459-41.

Editorial acknowledgement

Under direction of the authors, Katie Willetts, PhD, of Oxford PharmaGenesis, Oxford, UK provided medical writing support, which was funded by Novartis, in accordance with Good Publication Practice (GPP 2022) guidelines (https://www.ismpp.org/gpp-2022).

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

M.J. Morris: Financial Interests, Personal, Stocks/Shares: Doximity; Financial Interests, Personal, Advisory Role: Lantheus Medical Imaging, AstraZeneca, Amgen, Daiichi Sankyo, Convergent Therapeutics, Pfizer, ITM Isotope Technologies Munich, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Bipharma, Telix Pharmaceuticals, Progenics, Z-Alpha; Financial Interests, Institutional, Research Funding: Bayer, Progenics, Concept Therapeutics, Roche/Genentech, Janssen, Celgene, Novartis, Astellas Pharma; Financial Interests, Personal, Other: AstraZeneca, APCCC, Memorial Sloan-Kettering Cancer Center; Non-Financial Interests, Personal, Other: Bayer, Janssen Oncology, Novartis. A.J. Armstrong: Financial Interests, Institutional, Research Funding: Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen, Novartis; Financial Interests, Personal, Advisory Role: Astellas, Epic Sciences, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Clovis, Exact Sciences, Myovant, Exelixis, GoodRx, Novartis. K.N.N. Chi: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Point Biopharma, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Janssen, Novartis, Roche; Financial Interests, Institutional, Trial Chair: AstraZeneca, Arvinas, Janssen, Novartis; Financial Interests, Institutional, Local PI: Arvinas. J.S. de Bono: Financial Interests, Personal, Advisory Board: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi Sankyo, Eisai, Genentech Roche, Genmab, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals, Menarini Silicon Biosystems, ImCheck Therapeutics, Crescendo; Financial Interests, Institutional, Advisory Board: Harpoon; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayer, Cellcentric, Daiichi Sankyo, Genentech Roche, Genmab, GSK, Harpoon, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Sanofi Aventis, Sierra Oncology, Taiho, Vertex Pharmaceuticals, Crescendo Biologics, Menarini Silicon Biosystems; Non-Financial Interests, Principal Investigator: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi Sankyo, Eisai, Genentech Roche, Genmab, GSK, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals, Crescendo, ImCheck Therapeutics; Non-Financial Interests, Institutional, Product Samples: Daiichi Sankyo, Bayer, Merck Serono, AstraZeneca, Harpoon, Pfizer, Sierra Oncology, Genentech/Roche, Sanofi Aventis, GSK. 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Sartor: Financial Interests, Personal and Institutional, Research Grant: Advanced Accelerator Applications, Amgen, Janssen; Financial Interests, Personal, Advisory Role: ArtBio, Astellas, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant, Consultant: Bayer, Constellation; Financial Interests, Personal, Other, Consultant: Blue Earth Diagnostics, Clarity, Clovis, Convergent, Dendreon, EMD Serono, Foundation Medicine, Fusion, Hengrui, Isotopen Technologien Meunchen, Myovant, Theragnostics; Non-Financial Interests, Institutional, Research Grant: Endocyte; Non-Financial Interests, Personal, Other, Consultant: Genzyme, Invitae; Financial Interests, Personal and Institutional, Research Grant, consultant: Merck; Financial Interests, Personal, Other, consultant: Morphimmune, Myriad, Northstar, Novartis, Point Biopharma, Pfizer, Sanofi; Non-Financial Interests, Personal, Other, consultant: Noria Therapeutics Inc, Noxopharm, Tessa, Z-alpha; Non-Financial Interests, Personal and Institutional, Research Grant, consultant: Progenics; Financial Interests, Personal, Other, consultant, Equity Interest: RATIO; Non-Financial Interests, Personal and Institutional, Other, Grant research, consultant: Tenebio; Financial Interests, Personal, Other, consultant/Equity Interest: Telix. 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Wu: Financial Interests, Personal, Other, Employee: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. 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. All other authors have declared no conflicts of interest.