Abstract 1394P
Background
223Ra prolongs OS in pts with bone-predominant mCRPC. Here, we evaluated potential associations of ALP decline and pain response with OS during 223Ra treatment in the global, real-world REASSURE study, with the aim to define patient subgroups with different survival outcomes, which may help improve disease management strategies.
Methods
Pts treated with 223Ra were grouped by any ALP decline vs no decline and pain response vs no response, based on ALP levels at baseline (BL) and week 12 and the best pain response during 223Ra treatment. Pain levels were assessed using the Brief Pain Inventory-Short Form (BPI-SF). Cox proportional hazard models with 95% confidence intervals (CIs) were provided for associations between ALP decline and pain response with OS.
Results
Data were from 779 pts with ALP measurements at both BL and week 12. In total, 624 (80%) pts had a decline in ALP and 155 (20%) had no decline (Table). Pts with ALP decline had longer OS than pts with no decline (HR 0.739, 95% CI 0.601–0.916). For pts who had pain at BL (BPI-SF of ≥2) and ALP decline, OS was similar regardless of pain response (Table). In contrast, for pts with pain at BL and no ALP decline, OS was longer in pts with pain response than without (HR 0.498, 95% CI 0.322–0.768). For pts who had no pain at BL (BPI-SF of 0 or 1), OS was longer in pts who had ALP decline compared with those without (HR 0.581, 95% CI 0.354–1.007). Table: 1394P
| Variables | Patients (N) | Median OS (m) (95% CI) | HR (95% CI) |
| Any ALP decline vs No ALP decline* | 624 155 | 18.1 (17.0-19.5) 14.2 (12.3-16.4) | 0.739 (0.601-0.916) |
| Any ALP decline* and BL BPI-SF ≥2 Pain response vs No pain response | 279 149 | 17.8 (16.3-19.5) 17.0 (13.8-19.3) | 0.915 (0.717-1.173) |
| No ALP decline* and BL BPI-SF ≥2 Pain response vs No pain response | 62 53 | 16.2 (13.5-19.7) 10.9 (8.3, 14.7) | 0.498 (0.322-0.768) |
| No pain at BL (BPI-SF 0 or 1) Any ALP decline vs No ALP decline* | 134 28 | 22.4 (18.9-26.7) 20.3 (10.5-26.5) | 0.581 (0.354-1.007) |
*Measured at week 12 BL, baseline; BPI-SF, Brief Pain Inventory-Short Form; CI, confidence interval; HR, hazard ratio; m, months; N, number; OS, overall survival
Conclusions
ALP decline after 12 weeks of 223Ra treatment was associated with longer survival. In pts without ALP decline, pain response was associated with longer OS, compared with those without a pain response. The shortest OS was observed in pts with baseline pain, no ALP decline and no pain response, whilst the longest OS was seen for pts who had no pain at BL and had ALP decline.
Clinical trial identification
Editorial acknowledgement
Dr Chris Guise of Cancer Communications and Consultancy Ltd., Cheshire, UK, provided medical writing assistance, which was funded by Bayer. Dr Lila Adnane (Bayer) provided editorial assistance.
Legal entity responsible for the study
Bayer AG.
Funding
Bayer AG.
Disclosure
J. O'Sullivan: Financial Interests, Personal, Advisory Role: Bayer, Janssen, Astellas Pharma, Sanofi, Novartis; Financial Interests, Personal, Speaker’s Bureau: Bayer, Janssen, Novartis; Financial Interests, Institutional, Research Grant: Bayer. D. Heinrich: Financial Interests, Personal, Invited Speaker: AAA, a Novartis company, Astellas, Bayer, Bristol Myers Squibb, Ipsen, Janssen-Cilaq, Novartis, Sanofi-Aventis, EUSA Pharma; Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, EISAI, IPSEN, Janssen-Cilaq, Rohe, Organon Biosimilars; Financial Interests, Institutional, Invited Speaker, PROFOUND phase III trial, national coordinating investigator: AstraZeneca; Financial Interests, Institutional, Invited Speaker, CheckMate025 phase III trial, national coordinating investigator: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker, E7080-A001-111 phase Ib/II trial, national coordinating investigator: EISAI; Financial Interests, Institutional, Invited Speaker, SPARTAN phase III trial, national coordinating investigator: Janssen-Cilaq; Financial Interests, Institutional, Invited Speaker, Keynote 679 / ECHO 302 phase III trial, national coordinating investigator: Merck Sharp & Dome (MSD); Financial Interests, Institutional, Invited Speaker, TALAPRO-2 and TALAPRO-3 phase III trials, national coordinating investigator: Pfizer; Financial Interests, Institutional, Invited Speaker, IPATential150 phase III trial, national coordinating investigator: Roche; Non-Financial Interests, Leadership Role, Serving as the Chair of the Board (President) of the Norwegian Association of Oncology (NOF) since November 2019: Norwegian Association of Oncology; Non-Financial Interests, Advisory Role, Rapporteur on Actions against Cancer for CPME since February 2021: Standing Committee of European Doctors (CPME). E. Castro Marcos: Financial Interests, Personal, Advisory Role: Bayer, Janssen, AstraZeneca, Astellas Pharma, Merck, Pfizer, MSD Oncology; Financial Interests, Personal, Other, Travel/accommodation: Bayer, Janssen, Roche, Astellas Pharma, AstraZeneca; Financial Interests, Personal, Expert Testimony: Pfizer; Financial Interests, Personal, Other, Honoraria: Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer, Roche, Clovis Oncology; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer, Janssen, SYNLAB. S. George: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Bayer, Pfizer, Exelixis, Corvus Pharmaceuticals, Sanofi/Genzyme, EMD Serono, Seattle Genetics/Astellas, Eisai, Merck, AVEO, QED Therapeutics; Financial Interests, Institutional, Research Grant: Pfizer, Merck, Agensys, Novartis, Bristol Myers Squibb, Bayer, Eisai, Seattle Genetics/Astellas, Calithera Biosciences, Corvus Pharmaceuticals, Surface Oncology, Exelixis, Aravive, Aveo, Gilead Sciences. D.Y. Song: Financial Interests, Personal, Advisory Role: IsoRay Inc.; Financial Interests, Personal, Research Grant: BioProtect Inc., Bristol Myers Squibb-Celgene. S. Dizdarevic: Financial Interests, Personal, Advisory Role: GE Healthcare, Bayer. M. Essler: Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications, Bayer, Ipsen; Financial Interests, Personal, Other, Travel/accommodation: Ipsen. I.J. de Jong: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Other, Travel/accommodation: Bayer. P.G. Hammerer: Financial Interests, Personal, Advisory Role: Astellas Pharma, Ipsen, Janssen, Bayer. B. Tombal: Financial Interests, Personal, Advisory Role: Astellas Pharma, Bayer, Ferring, Janssen, Takeda, Steba Biotech, Sanofi, Myovant Sciences, Pfizer/Astellas; Financial Interests, Personal, Speaker’s Bureau: Amgen, Janssen, Astellas Pharma; Financial Interests, Personal, Other, Travel/accommodation: Amgen, Astellas Pharma, Bayer, Ferring, Janssen, Sanofi; Financial Interests, Personal, Expert Testimony: Tookad; Financial Interests, Personal, Other, Honoraria: Amgen, Astellas Pharma, Bayer, Ferring, Sanofi, Janssen, Myovant Sciences; Financial Interests, Institutional, Research Grant: Ferring. N.D. James: Financial Interests, Personal, Advisory Role: Sanofi, Bayer, Astellas Pharma, Janssen, Clovis Oncology, EUSA pharma, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre, Ferring, Sanofi, Astellas Pharma, Janssen Oncology, Merck, AstraZeneca; Financial Interests, Personal, Other, Travel/accommodation: Sanofi, Janssen; Financial Interests, Personal, Other, Honoraria: Sanofi, Bayer, Janssen, Astellas Pharma; Financial Interests, Institutional, Research Grant: Janssen, Astellas Pharma, Pfizer, Sanofi, Novartis, AstraZeneca. F. Verholen: Financial Interests, Personal, Full or part-time Employment: Bayer; Financial Interests, Personal, Other, Travel/accommodation: Bayer. J. Meltzer: Financial Interests, Personal, Full or part-time Employment: Bayer; Financial Interests, Personal, Stocks/Shares, Myself and an immediate family member: Bayer, Pfizer, Lilly. P. Sandström: Financial Interests, Personal, Full or part-time Employment: Bayer. O. Sartor: Financial Interests, Personal, Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Constellation Pharmaceuticals, Advanced Accelerator Applications, Pfizer, Bristol Myers Squibb, Bavarian Nordic, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant Sciences, Myriad Genetics, Novartis, Clarity Pharmaceuticals, Fusion Pharmaceuticals, Isotopen Technologien, Janssen, Noxopharm, Clovis Oncology, Noria Therapeutics, Point Biopharma, TeneoBio, Telix Pharmaceuticals, Theragnostics; Financial Interests, Personal, Other, Travel/accommodation: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Stocks/Shares: Lilly, GlaxoSmithKline, AbbVie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Clovis Oncology; Financial Interests, Institutional, Research Grant: Bayer, Sanofi, Endocyte, Merck, InVitae, Constellation Pharmaceuticals, Advanced Accelerator Applications, AstraZeneca, Dendreon; Financial Interests, Personal, Research Grant: SOTIO, Janssen. All other authors have declared no conflicts of interest.