Abstract 1611P
Background
In PSMAfore (NCT04689828), [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged rPFS versus androgen receptor pathway inhibitor (ARPI) change with a favourable safety profile in taxane-naive patients with metastatic castration-resistant prostate cancer (mCRPC). We report the incidence, risk factors and management of haematologic treatment emergent adverse events (TEAEs).
Methods
Adults with PSMA-positive mCRPC and one progression on prior ARPI were randomized 1:1 to 177Lu-PSMA-617 (7.4 GBq Q6W; 6 cycles) or ARPI change. The primary endpoint was rPFS; secondary endpoints included frequency of TEAEs and safety laboratory assessments. Haematologic TEAEs (CTCAE v5.0 coding) were grouped by MedDRA v26.1 terms. Baseline metastatic bone disease was assessed by bone scan. Baseline, on-treatment and follow-up haematology were assessed. The safety analysis set and 27 February 2024 data cutoff (third interim OS analysis) were used.
Results
Incidences of haematologic TEAEs were higher among patients receiving 177Lu-PSMA-617 than ARPI change (Table). For 177Lu-PSMA-617 versus ARPI change, haematologic TEAE incidences were 33/109 (30.3%) versus 22/113 (19.5%) in patients with ≤5 metastatic bone lesions and 53/118 (44.9%) versus 32/119 (26.9%) in patients with >5 bone lesions; incidence did not increase for patients receiving 5/6 versus 1–4 doses of 177Lu-PSMA-617. For 177Lu-PSMA-617 versus ARPI change: 29 patients (12.8%) versus 28 (12.1%) received blood transfusions (on-treatment: 19 [8.4%] vs 26 [11.2%]); 4 (1.8%) versus 3 (1.3%) received erythropoietin; 3 (1.3%) versus 0 received granulocyte colony stimulating factors.
Conclusions
Despite higher incidences of haematologic TEAEs among patients receiving 177Lu-PSMA-617 compared with ARPI change, rates of complications or need for management of haematologic TEAEs were low and similar between treatment arms. Table: 1611P
177Lu-PSMA-617n=227 | ARPI changen=232 | |||
All grades | Gr ≥3 | All grades | Gr ≥3 | |
Pts with ≥1 event, n (%) a | 86 (37.9) | 30 (13.2) | 54 (23.3) | 20 (8.6) |
Anaemia & haemoglobin decreased | 63 (27.8) | 14 (6.2) | 45 (19.4) | 16 (6.9) |
Thrombocytopenia & platelet count decreased | 23 (10.1) | 7 (3.1) | 9 (3.9) | 2 (0.9) |
Neutropenia & neutrophil count decreased & febrile neutropenia | 18 (7.9)b | 5 (2.2)b | 5 (2.2)c | 2 (0.9)c |
Lymphopenia & lymphocyte count decreased | 15 (6.6) | 10 (4.4) | 3 (1.3) | 1 (0.4) |
Leukopenia & white blood cell count decreased | 14 (6.2) | 3 (1.3) | 3 (1.3) | 1 (0.4) |
Pancytopenia | 1 (0.4) | 0 | 1 (0.4) | 0 |
DCO 27 Feb 2024aRelated TEAEs as reported in the CRF are combined; patients are counted once per preferred term Febrile neutropenia: bn=2; cn=0
Clinical trial identification
NCT04689828, Protocol release date: 21 Feb 2023.
Editorial acknowledgement
Under direction of the authors, Katie Willetts, 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.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. O. Sartor: Financial Interests, Personal, Writing Engagement: Novartis; Financial Interests, Institutional, Research Grant: AAA, Amgen, AstraZeneca, Bayer, Endocyte, Invitae, Janssen, Lantheus, Merck, Progenics, and Tenebio; Financial Interests, Personal, Speaker, Consultant, Advisor: ARTBIO, AAA, AstraZeneca, Bayer, Blue Earth Diagnostics, Clarity Pharmaceuticals, Fusion, Isotopen Technologien Muenchen, Merck, Janssen, Myovant, Myriad, Noria Therapeutics, Novartis, NorthStar, POINT Biopharma, Pfizer, Sanofi, Tenebio, and Telix; Financial Interests, Personal, Other: Lantheus, Novartis, and NorthStar;; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, and Pfizer; Financial Interests, Personal, Stocks or ownership: Artbio, Ratio, Clarity, Convergent, Fusion, Lilly, Pfizer, Telix. 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. 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, MetaCurUm, Myricx, Nurix Therapeutics, Oncternal Therapeutics; Financial Interests, Institutional, Advisory Board: Harpoon, Dark Blue Therapeutics, Novartis, Takeda, Tango Therapeutics; 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, Immunic Therapeutics, MetaCurUm, Myricx, Nurix Therapeutics, Oncternal Therapeutics; Financial Interests, Institutional, Local PI: Amgen; 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, Immunic Therapeutics; Non-Financial Interests, Institutional, Product Samples: Daiichi Sankyo, Bayer, Merck Serono, AstraZeneca, Harpoon, Pfizer, Sierra Oncology, Genentech/Roche, Sanofi Aventis, GSK. 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. 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: Y-mAbs; Financial Interests, Personal, Advisory Board, Scientific Advisor: AdvanceCell; Financial Interests, Personal, Advisory Board, Advisor, Consultant: Janssen; Financial Interests, Personal, Advisory Board, Consultant: Eco1R, Fusion Pharmaceuticals, Genentech; Financial Interests, Personal, Member of Board of Directors: Sofie Biosciences, Pharma 15; Financial Interests, Personal, Ownership Interest: Sofie Biosciences; Financial Interests, Personal, Stocks/Shares: Aktis Oncology, AdvanCell, Convergent Therapeutics; Non-Financial Interests, Leadership Role, Chair Oncology&Theragnostics Committee: EANM. 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. J.M. Piulats Rodriguez: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Roche, BMS, MSD, BeiGene, VCN, AstraZeneca, Immunocore, Novartis; Financial Interests, Personal and Institutional, Research Grant: BMS, Pfizer, Janssen, BeiGene, Mirati, Immunocore, Regeneron. A. Flechon: Financial Interests, Personal, Ownership Interest: Janssen, Novartis, Adacap, Bayer, Astellas, Pfizer, AstraZeneca. X.X. Wei: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Membership on Biomarker/Immune Response Monitoring Committee (BIRMC): Dendreon; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb; Non-Financial Interests, Advisory Role: MacroGenics, MacroGenics; Non-Financial Interests, Principal Investigator: Barinthus Biotherapeutics, MacroGenics, Novartis, Poseida. H. Kim: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor, Research, Speaker fees and travel: Varian; Financial Interests, Personal, Ownership Interest: GlobalART. M. Schweizer: Financial Interests, Personal, Advisory Board: Sanofi, AstraZeneca; Financial Interests, Personal, Other, Consultant: PharmaIn; Financial Interests, Institutional, Local PI: Zenith Epigenetics, BMS, Merck, Janssen, Pfizer, F. Hoffmann-La Roche, Tmunity, Epigenetix, Incyte, Ambrx Inc.; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Signal One. S. Alanee: Financial Interests, Personal, Full or part-time Employment: Novartis Oncology. S. Ghebremariam: Financial Interests, Personal, Full or part-time Employment: Novartis Oncology. M. Hertelendi: Financial Interests, Personal, Full or part-time Employment: Novartis Oncology. M.J. Morris: Financial Interests, Personal, Advisory Board: Oric, Pfizer, Exelixis, Lantheus, AstraZeneca, Amgen, Daiichi Sankyo, Convergent, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, Z-alpha; Financial Interests, Personal, Invited Speaker: Progenics, ITM Isotope Technologies; Financial Interests, Personal, Stocks/Shares: Doximity; Financial Interests, Institutional, Coordinating PI: Novartis, Celgen; Financial Interests, Institutional, Local PI: Corcept, Janssen, Astellas; Non-Financial Interests, Advisory Role: Bayer, Janssen Oncology, Novartis; Other, Travel to conference: AstraZeneca; Other, Travel/lodging at conference: APCCC.
Resources from the same session
1199P - Developing and systematically validating homologous recombination repair gene detection method based on next-generation sequencing
Presenter: Yi Sun
Session: Poster session 10
1200P - Investigation of multiphoton microscopy as an innovative tool for intraoperative section-free histologic investigations in just a few minutes
Presenter: Martí Homs Soler
Session: Poster session 10
1201P - Novel deep learning model and validation of whole slide images in lung cancer diagnosis
Presenter: Alhassan Ahmed
Session: Poster session 10
Resources:
Abstract
1202P - A deep learning approach using routine pathology images to guide precision medicine in metastatic CRC
Presenter: Chaitanya Parmar
Session: Poster session 10
1203P - Analytical evaluation of whole genome sequencing for acute myeloid leukemia
Presenter: Guidantonio Malagoli Tagliazucchi
Session: Poster session 10
1204P - Real-world utility of whole genome sequencing for patients with cancer: Evaluation of a regional implementation of the 100,000 genomes project
Presenter: Helen Robbins
Session: Poster session 10
1205P - A retrospective machine learning-based analysis of nationwide cancer CGP data across cancer types to identify features associated with recommendation of mutation-based therapy
Presenter: Hiroaki Ikushima
Session: Poster session 10
1478P - Dual single-nucleotide polymorphism biomarker combination to select opioid for cancer pain management
Presenter: Yoshihiko Fujita
Session: Poster session 10
1479P - Use of rescue opioids and pain control after ketamine initiation in refractory cancer pain: A multicentric observational study
Presenter: Pablo Gallardo Melo
Session: Poster session 10
1480P - Long term therapy with denosumab and zoledronic acid: A comparative real-world retrospective observational study on skeletal-related events and pain in patients with metastatic breast cancer
Presenter: Giacomo Massa
Session: Poster session 10