1599P - Symptomatic skeletal events, health-related quality of life and pain in a phase III study of [177Lu]Lu-PSMA-617 in taxane-naive patients with PSMA-positive metastatic castration-resistant prostate cancer: Third interim analysis of PSMAfore

Background

In PSMAfore (NCT04689828), [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) prolonged rPFS versus androgen receptor pathway inhibitor (ARPI) change in taxane-naive patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). We now present the time to symptomatic skeletal events (SSE) and time to worsening (TTW) in health-related quality of life (HRQoL) and pain at the third interim analysis (data cutoff, 27 Feb 2024).

Methods

Eligible patients had mCRPC, were candidates for ARPI change after one progression on previous ARPI, and had ≥1 PSMA-positive and no exclusionary PSMA-negative metastatic lesions by [⁶⁸Ga]Ga-PSMA-11 PET/CT. Patients were randomized 1:1 to open-label ¹⁷⁷Lu-PSMA-617 (7.4 GBq q6w; 6 cycles) or ARPI change (abiraterone/enzalutamide). Patients with confirmed radiographic progression on ARPI change could cross over to ¹⁷⁷Lu-PSMA-617. The primary endpoint was rPFS. Other endpoints included time to SSE and TTW in self-reported HRQoL (FACT-P, EQ-5D-5L; secondary) and pain (BPI-SF; exploratory).

Results

In total, 468 patients (234/arm) were randomized. Median duration of exposure was 8.4 months for ¹⁷⁷Lu-PSMA-617 and 6.5 months for ARPI change. ¹⁷⁷Lu-PSMA-617 prolonged time to SSE and fewer bone fractures were reported versus ARPI change (4 [1.7%] vs 13 [5.6%]) (Table). ¹⁷⁷Lu-PSMA-617 prolonged TTW in FACT-P, EQ-5D-5L and BPI-SF versus ARPI change (Table). Incidences of grade ≥3 adverse events (AEs), serious AEs and AEs leading to discontinuation for ¹⁷⁷Lu-PSMA-617 and ARPI change were 36% and 48%, 20% and 32%, and 5.7% and 5.2%, respectively. Table: 1599P

DCO, 27 Feb 2024NE, not estimable

Conclusions

¹⁷⁷Lu-PSMA-617 clinically meaningfully and significantly prolonged time to SSE and TTW in self-reported HRQoL and pain versus ARPI change in taxane-naive patients with PSMA-positive mCRPC.

Clinical trial identification

NCT04689828.

Editorial acknowledgement

Under direction of the authors, Sophie Adams, PhD, of Oxford PharmaGenesis, Oxford, UK provided medical writing support, which was funded by Novartis.

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

K. Fizazi: Financial Interests, Personal and Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Arvinas, CureVac, Macrogenics, Orion; Financial Interests, Personal, Advisory Board: Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis, Pfizer, Sanofi. M.J. Morris: Financial Interests, Institutional, Research Grant: Bayer; Progenics; Corcept Therapeutics; Roche/Genentech; Janssen; Celgene; Novartis; Astellas Pharma; Financial Interests, Personal, Speaker, Consultant, Advisor: Lantheus Medical Imaging, AstraZeneca, Amgen, Daiichi Sankyo, Convergent Therapeutics, Pfizer, ITM Isotope Technologies Munich, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix Pharmaceuticals, Progenics, and Z-Alpha; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca, APCCC, and Memorial Sloan-Kettering Cancer Center; Financial Interests, Personal, Stocks/Shares: Doximity. N.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Cold Genesys, Dendreon, Exact Imaging, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, Sanofi Genzyme, Speciality Networks, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Asieris, Alessa Therapeutics, Arquer, Fize medical, GConcology, Guardant, Ferring, Foundation Medicine, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Promaxo, Protara, Accord, Antev, Aura biosciences, Sumitomo; Financial Interests, Personal, Member of Board of Directors: Photocure, Alessa Theraputics; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Bayer, Aura, Exact Imaging, Janssen, Merck, Myovant, Novartis, Pfizer, Propella, Bristol Myers Squibb, Dendreon, Pfizer, Urogen; Financial Interests, Institutional, Local PI: alessa, GC oncology, FORMA therapeutics, Pacific edge, Point Biopharma, The MT group, Theralase, Verity, Astellas, Palette Life Sciences, Steba, Zenflow. 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Crosby: Financial Interests, Personal, Steering Committee Member: Novartis; Financial Interests, Personal, Other, Consulting fees: Lantheus; Financial Interests, Personal, Other, Patient Advocacy Support Pfizer Patient Advocacy Support: Pfizer; Financial Interests, Personal, Other, Patient Advocacy Support Pfizer Patient Advocacy Support Pfizer Patient Advocacy Support: Johnson & Johnson; Financial Interests, Personal, Other, Patient Advocacy Support Pfizer Patient Advocacy Support: Sumitomo; Financial Interests, Personal, Other, Patient Advocacy Support: Astellas, AstraZeneca, BlueEarth Diagnostics, Boston Scientific, Elekta, Macrogenitcs, Profound Medical, Telix, Tempus, Tolmar; Financial Interests, Personal and Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Telix; Financial Interests, Personal and Institutional, Advisory Board, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Profind Medical, Pfizer, Johnson & Johnson; Financial Interests, Personal, Advisory Board: Telix; Financial Interests, Personal and Institutional, Advisory Board: Society of Nuclear Medicine and Molecular Imagin; Financial Interests, Personal and Institutional, Steering Committee Member: American Urological Association. 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Roubaud: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Bayer; Financial Interests, Institutional, Advisory Board: Pfizer, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Coordinating PI: Bayer. J. Nagarajah: Financial Interests, Personal and Institutional, Research Grant: Novartis, ABX; Financial Interests, Personal, Speaker, Consultant, Advisor: CURIUM, POINT Biopharma; Financial Interests, Personal and Institutional, Other, Payment of honoraria for lectures, presentations, speakers bureaus, manuscript writing, educational events: Bayer, AG, Pfizer. M.T. Fleming: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis. D.E. Castellano Gauna: Financial Interests, Personal, Advisory Board: Pfizer, Roche, BMS, Janssen, Astellas, MSD, Ipsen, AstraZeneca, Novartis, GSK; Financial Interests, Institutional, Local PI: Pfizer, Roche, MSD, BMS, AstraZeneca, Janssen, Astellas, Ipsen, Exelisis, Eisai, Lilly, Bayer, GSK, Clovis, QED Therapeutics; Non-Financial Interests, Other, any: Associate Professor of Medical Oncology/Internal Medicine department; Non-Financial Interests, Personal, Other, Executive member: SOGUG (Spanish Oncology Genito-Urinary Group) Foundation; Non-Financial Interests, Personal, Training, Head of GU Alliance for Research and Development Consortium: GUARD Consortium; Other, any: Member of the Internal/local Pharmacy Commission at the Hospital Universitario 12 de Octubre. N. Carnahan: Financial Interests, Institutional, Full or part-time Employment: Novartis Pharmaceuticals. S. Ghebremariam: Financial Interests, Personal, Full or part-time Employment: Novartis. M. Hertelendi: Financial Interests, Personal, Full or part-time Employment: Novartis. O. Sartor: Financial Interests, Personal, Other, All support for the present manuscript: Novartis; Financial Interests, Institutional, Research Grant: Novartis, Amgen, Bayer, Endocyte, Invitae, Janssen, Lantheus, Merck, Progenics, Tenebio; Financial Interests, Institutional, Royalties: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: ARTBIO, AAA, AstraZeneca, Bayer, Blue Earth Diagnostics, Clarity Pharmaceuticals, Fusion, Isotope Technologies, Merck, Janssen, Myovant, Myriad, Noria Therapeutics, Novartis, NorthStar, POINT Biopharma, Pfizer, Sanofi, Tenebio, Telix; Financial Interests, Personal, Other, Support for attending meetings and travel: Lantheus, Novartis, NorthStar; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, Pfizer; Financial Interests, Personal, Stocks/Shares: ARTBIO, Ratio, Clarity Pharmaceuticals, Convergent, Fusion, Pfizer, Telix; Financial Interests, Personal, Stocks or ownership: Lilly. All other authors have declared no conflicts of interest.