Abstract 1810P
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
Mediana TTW in FACT-P score, months (95% CI) | |||||
Total | Physical wellbeing | Emotional wellbeing | Social/family wellbeing | Functional wellbeing | |
PSA decline up to week 12 b , % | |||||
0 (n = 104) | 3.3 (2.5, 3.9) | 2.3 (2.0, 3.3) | 3.3 (3.0, 4.5) | 3.5 (3.2, 4.4) | 3.2 (2.3, 3.9) |
≤ 50 (n = 62) | 6.2 (4.6, 7.9) | 4.7 (3.3, 7.8) | 7.1 (4.6, 9.1) | 6.7 (5.1, 9.1) | 4.6 (1.9, 5.7) |
> 50 to ≤ 90 (n = 113) | 8.0 (6.4, 10.7) | 8.8 (6.2, 10.6) | 8.4 (6.7, 10.7) | 8.0 (6.3, 10.6) | 7.0 (4.6, 8.6) |
> 90 (n = 61) | 11.3 (6.9, 15.6) | 10.2 (4.6, 14.6) | 15.6 (9.3, 18.4) | 8.8 (5.3, 15.1) | 7.8 (2.6, 11.5) |
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. K. Herrmann: Financial Interests, Personal, Advisory Board: Bayer, Adacap/Novartis, Curium, Boston Scientific, GE Healthcare, AstraZeneca; Financial Interests, Personal, Invited Speaker: Sirtex, Siemens Healthineers, Monrol; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, DMSB: ymabs; Financial Interests, Personal, Advisory Board, Scientific Advisor: AdvanceCell; Financial Interests, Personal, Advisory Board, Advisor, Consultant: Janssen; Financial Interests, Personal, Advisory Board, Consultant: Eco1R; Financial Interests, Personal, Member of Board of Directors: Sofie Biosciences, Theragnostics, Pharma 15; Financial Interests, Personal, Ownership Interest: Sofie Biosciences; Financial Interests, Personal, Stocks/Shares: Aktis Oncology; Non-Financial Interests, Leadership Role, Chair Oncology&Theragnostics Committee: EANM. B. Krause: Financial Interests, Personal, Invited Speaker: Astellas, Bayer Vital; Financial Interests, Institutional, Principal Investigator: Endocyte; Financial Interests, Personal, Advisory Role: ITM, PSI CRO; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal and Institutional, Advisory Board, Invited speaker, consulting fees, PI: Novartis; Financial Interests, Personal, Advisory Board, consulting fees: Terumo. K. Rahbar: Financial Interests, Personal and Institutional, Advisory Role: ABX, Bayer; Financial Interests, Personal and Institutional, Advisory Board, lectureship payments: AAA; Financial Interests, Personal, Other, lectureship payments: AstraZeneca, Janssen Cielag Amgen; Financial Interests, Personal, Advisory Role: ABX CRO Pharmtrace. O. 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. S.T. Tagawa: Financial Interests, Personal, Advisory Board: Convergent Therapeutics, AIkido Pharma; Financial Interests, Personal, Other, Consultant: EMD Serono, Telix Pharma, Blue Earth Diagnostics, POINT Biopharma, Myovant, Bayer, 4D Pharma, Gilead, Pfizer, Janssen, Astellas, AbbVie, Novartis, Seagen, Clarity, Merck, Myovant, EMD Serono; Financial Interests, Personal, Stocks/Shares: AIkido Pharma; Financial Interests, Personal, Other, Patent co-inventor: Gilead; Financial Interests, Institutional, Local PI: Medivation, Astellas, Janssen, Amgen, BMS, AstraZeneca, Bayer, Merck, Clovis, Seagen; Financial Interests, Institutional, Steering Committee Member: Gilead, Novartis, POINT Biopharma, Clarity, Ambrx, Promontory. J. Nagarajah: Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Personal, Advisory Role: Curium. X.X. Wei: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Coordinating PI: BMS. V.S. Koshkin: Financial Interests, Personal, Advisory Board: Janssen, Clovis, Astellas, AstraZeneca, Pfizer, EMD Serono; Financial Interests, Personal, Other, Consulting: GLG, ExpertConnect, Guidepoint; Financial Interests, Institutional, Local PI: Merck, Taiho, Eli Lilly, Clovis, Novartis; Financial Interests, Institutional, Steering Committee Member: Seagen; Financial Interests, Personal and Institutional, Research Grant: Prostate Cancer Foundation. F. Saad: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Sanofi, Pfizer, Myovant, Novartis, AstraZeneca, Merck, Myovant; Financial Interests, Institutional, Local PI: Novartis, Astellas, Bayer, Janssen, Sanofi, BMS, Amgen, Pfizer, Merck; Financial Interests, Institutional, Coordinating PI: AstraZeneca. A. Vickers: Other, Institutional, Other, Conducted research: Advanced Accelerator Applications. R. Ghouse: Financial Interests, Personal, Other, Employee: Novartis. J. 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.
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