Abstract 1372P
Background
In the phase 3 VISION trial, lutetium (177Lu) vipivotide tetraxetan ([177Lu]Lu-PSMA-617; 177Lu-PSMA-617) prolonged radiographic progression-free survival (rPFS) and overall survival (OS) when added to protocol-permitted standard of care (SoC) in patients with progressive, PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). The proportion of patients with confirmed decline from baseline in prostate-specific antigen (PSA) level ≥ 50% was higher with 177Lu-PSMA-617 plus SoC treatment than with SoC alone. This post hoc, exploratory analysis aimed to evaluate associations between magnitude of PSA decline from baseline and clinical outcomes in the 177Lu-PSMA-617 group.
Methods
Patients in the 177Lu-PSMA-617 group were classified into four subgroups by magnitude of confirmed best PSA decline from baseline: no decline; ≤ 50% decline; > 50 – ≤ 90% decline; and > 90% decline (cut-off date: 27 January 2021). PSA levels were assessed at baseline and at the start of each six-weekly treatment cycle. Median OS and rPFS were estimated with the Kaplan–Meier method. Hazard ratios (HRs) were estimated using Cox proportional-hazards regression.
Results
Greater PSA decline from baseline was associated with prolonged rPFS and OS in the 177Lu-PSMA-617 group (Table). Patients with PSA declines > 50 – ≤ 90% and > 90% had an 80% and 96% reduced risk of radiographic disease progression, and a 58% and 90% reduced risk of death, respectively, versus those with no decline. Landmark analyses will also be presented. Table: 1372P
Clinical outcomes by PSA decline subgroups with 177Lu-PSMA-617
| Best overall PSA decline | |||||
| Outcome | No decline | > 0 – ≤ 50% | > 50 – ≤ 90% | > 90% | |
| rPFS a n = 385 | n (%) | 97 (25.2) | 53 (13.8) | 88 (22.9) | 106 (27.5) |
| Median, months (95% CI) | 3.0 (2.4, 3.7) | 6.0 (4.2, 8.6) | 8.8 (8.5, 10.8) | 19.7 (17.0, 20.6) | |
| HR (95% CI)c | 1.0 (reference) | 0.40 (0.26, 0.60) | 0.20 (0.14, 0.30) | 0.04 (0.02, 0.08) | |
| OS b n = 551 | n (%) | 147 (26.7) | 79 (14.3) | 112 (20.3) | 157 (28.5) |
| Median, months (95% CI) | 8.4 (7.3, 9.5) | 12.0 (10.3, 14.0) | 15.0 (13.9, 17.8) | NE (26.8, NE) | |
| HR (95% CI)c | 1.0 (reference) | 0.58 (0.43, 0.79) | 0.42 (0.32, 0.56) | 0.10 (0.07, 0.15) |
aAnalysis in PFS-FAS; bAnalysis in FAS; cHR of PSA decline vs no decline. FAS, full analysis set; NE, not estimable.
Conclusions
In this analysis, the magnitude of PSA decline from baseline was strongly associated with prolonged rPFS and OS in patients with mCRPC treated with 177Lu-PSMA-617 plus SoC. This suggests that PSA decline is of prognostic importance for clinical outcomes during radioligand therapy with 177Lu-PSMA-617 in this patient population.
Clinical trial identification
NCT03511664, 30 April 2018.
Editorial acknowledgement
Under the guidance of the authors, Karim Bensaad, PhD from Oxford PharmaGenesis (Oxford, UK) provided medical writing support for this abstract, with funding from Advanced Accelerator Applications, a Novartis Company.
Legal entity responsible for the study
Advanced Accelerator Applications, a Novartis Company.
Funding
Advanced Accelerator Applications, a Novartis Company.
Disclosure
A.J. Armstrong: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Pfizer, AstraZeneca, Forma, Exelixis, Myovant, Dendreon, Clovis, Epic Sciences, Exact Sciences, Janssen, Bayer; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, MSD, Pfizer, AstraZeneca, Forma, Exelixis, Myovant, Dendreon, Clovis, Genentech/Roche, Amgen, Janssen, Bayer. O. Sartor: Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Blue Earth Diagnostics, Inc., Bavarian Nordic, Bristol Myers Squibb, Clarity Pharmaceuticals, Clovis, Constellation, Dendreon, EMD Serono, Fusion, Isotopen Technologien Meunchen, Janssen, Myovant, Myriad, Noria Therapeutics, Inc., Novartis, Noxopharm, Progenics, POINT Biopharma, Pfizer, Sanofi, Tenebio, Telix, Theragnostics; Financial Interests, Institutional, Research Grant: Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Constellation, Endocyte, Invitae, Janssen, Lantheus, MSD, Progenics, Tenebio. F. Saad: Financial Interests, Personal, Advisory Role: Janssen, Bayer, Myovant, Astellas, BMS, Novartis, Sanofi, Astrazenca; Financial Interests, Institutional, Research Grant: Janssen, Bayer, Myovant, Astellas, BMS, Novartis, Sanofi, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Janssen, Bayer, Myovant, Astellas, BMS, Novartis, Sanofi, Astraz. J. Czernin: Financial Interests, Personal, Advisory Board, I am was on a medical advisory Board: Amgen; Financial Interests, Personal, Advisory Board, I am a medical advisory board member: Rayze Bio; Financial Interests, Personal, Stocks/Shares, Founder of Sofie Biosciences. I also am a board member: Sofie Biosciences; Financial Interests, Personal, Other, I am a founder. I do not receive any financial compensation: Trethera Corporation. N.D. Shore: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Institutional, Research Grant: Novartis. A.T. Kendi: Financial Interests, Personal, Advisory Board, Prostate, LuPSMA: Novartis; Financial Interests, Institutional, Principal Investigator, VISION study, PI for Mayo Clinic Rochester: Novartis. T.M. Beer: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, Arvinas, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Clovis Oncology, Constellation, Dantari Pharmaceuticals, GlaxoSmithKline, Grail Inc., Janssen, Myovant Sciences, Novartis, Pfizer, Sanofi, Sapience Therapeutics, Tolero; Financial Interests, Institutional, Research Grant: AllianceFoundation Trials, Astellas Pharma, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Endocyte Inc., Exact Sciences Corp., Freenome, Grail Inc., Harpoon Therapeutics, Janssen, Medivation Inc., MSD, Sotio, Theraclone Sciences/OncoResponse, Zenith Epigenetics; Financial Interests, Personal, Stocks/Shares: Arvinas Inc., Salarius Pharmaceuticals. N. Vaishampayan: Financial Interests, Personal, Advisory Board, Reporting for Spouse: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Reporting for spouse: Exelixis, Pfizer, Bayer, Merck, Aveo, Sonofi; Financial Interests, Personal, Advisory Role, Reporting for spouse: AAA; Financial Interests, Personal, Advisory Board: Novartis. G. El-Haddad: Financial Interests, Personal, Advisory Role: Novartis, Canon Medical, Curium pharma, Boston Scientific, Terumo, Bayer; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Wu: Financial Interests, Personal, Stocks/Shares: Novartis. O. Mirante: Financial Interests, Personal, Stocks/Shares: Novartis. M.J. Morris: Financial Interests, Personal, Advisory Board: Oric, Pfizer, Exelixis, Lantheus, AstraZeneca, Amgen, Daiichi, Convergent; Financial Interests, Personal, Stocks/Shares: Doximity; Financial Interests, Institutional, Invited Speaker: Novartis, Corcept, Celgen, Janssen.