1816P - Combination treatment with radium-223 (223Ra) and enzalutamide (enza) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in the REASSURE study

Background

²²³Ra and enza both prolong overall survival (OS) in pts with mCRPC. Their different mechanisms of action and non-overlapping safety profiles make them attractive combination partners. Here, we present clinical outcomes of pts who received combined or layered treatment with ²²³Ra and enza in REASSURE (NCT02141438), a global, prospective, observational study of ²²³Ra use in pts with mCRPC.

Methods

Data from 1,465 pts (All pts) were analysed. Pt subgroups included “combined” (pts started ²²³Ra and enza within 30 days of each other, n=46) and “layered” (pts started ²²³Ra >30 days after starting enza or vice versa, n=205). Statistics were descriptive in nature.

Results

The proportions of pts who had completed ≥1 life-prolonging therapy for mCRPC prior to ²²³Ra were 43%, 52% and 61% in the combined, layered and All pts groups, respectively (30%, 27% and 33% had received prior abiraterone and 17%, 29% and 36% had received prior docetaxel, respectively). More pts in the combined group (74%) completed 6 cycles of ²²³Ra than in the layered (61%) or All pts (59%). Median duration of observation from start of ²²³Ra for combined, layered and All pts was 17.3, 11.1 and 11.5 months (mo), respectively. The proportions of pts with a ≥30% decline in alkaline phosphatase at week-12 were 58%, 41% and 47% in the combined, layered and All pts groups, respectively; corresponding values for a ≥30% decline in prostate specific antigen were 54%, 17% and 20%. Median OS was 22.2 mo (95% CI 13.7–26.8) in the combined group, 16.5 mo (95% CI 13.9–19.5) in the layered group and 15.6 mo (95% CI 14.6–16.5) in All pts. Table: 1816P

Summary of safety

Conclusions

When combined or layered with enzalutamide, treatment with ²²³Ra was not associated with new safety signals and did not appear to increase fracture risk. Median OS was numerically longer in the combined vs the layered group or All pts. A phase 3 trial (PEACE III, NCT02194842) investigating the combination of enza with ²²³Ra is ongoing.

Clinical trial identification

NCT02141438.

Editorial acknowledgement

Dr Chris Guise of Cancer Communications and Consultancy Ltd, Cheshire, UK, provided medical writing assistance (funded by Bayer). Dr Lila Adnane (Bayer) provided editorial assistance.

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Disclosure

B. Tombal: Financial Interests, Personal, Advisory Board: 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, expenses: 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, Pfizer, Myovant Sciences; Financial Interests, Institutional, Research Funding: Ferring. P.J. Goebell: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, BMS, Clinsol, Eisai, EUSA, iOMedico, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi; Financial Interests, Personal, Other, Honoraria: Astellas, AstraZeneca, Bayer, BMS, Clinsol, Eisai, EUSA, iOMedico, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, Apogepha; Financial Interests, Personal, Other, Travel, accommodation and expenses: Astellas, AstraZeneca, Bayer, BMS, Clinsol, Eisai, EUSA, iOMedico, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, Apogepha. N.D. Shore: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boston Scientific, Clarity, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Foundation Medicine, Genesis Care, Invitae, Janssen, Lantheus, Eli Lilly, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Phosphorous, Photocure, Propella, PreView, Sanofi Genzyme, Sema4, Speciality Networks, Sesen Bio, Telix, Tempus, Tolmar, Urogen, Vaxiion; Financial Interests, Personal, Expert Testimony: Ferring. D.J. George: Financial Interests, Personal, Other, Grants and/or fees: Acerta Pharma, the American Association for Cancer Research, Astellas, AstraZeneca, Axess Oncology, Bayer, BMS, Calithera, Capio Biosciences, EMD Serono, Exelixis, Flatiron, Ipsen, UroGPO, Janssen, Leidos Biomedical Research, Merck Sharp & Dohme, Michael J Hennessey Associates, Millennium Med Publishing, Modra Pharmaceuticals, Myovant Sciences, NCI, Nektar Therapeutics, Novartis, Pfizer, Physician Education Resource, Sanofi, UroToday, Vizuri Health Sciences. A. Pinto: Financial Interests, Personal, Advisory Role: Astellas, Janssen, Bayer, Clovis, Sanofi, Pfizer, Novartis, BMS, Roche, MSD, Pierre-Fabre, Ipsen; Financial Interests, Personal, Other, Travel grant: Pfizer, Janssen, Roche. O. Sartor: Financial Interests, Personal, Advisory Role: Bayer, Sanofi, AstraZeneca, Dendreon, Advanced Accelerator Applications, Pfizer, EMD Serono, Astellas Pharma, Progenics, Blue Earth Diagnostics, Myovant Sciences, Myriad Genetics, Novartis, Clarity Pharmaceuticals, Fusion Pharmaceuticals, Isotopen Technologien, Janssen, Clovis Oncology, Noria Therapeutics, Point Biopharma, TeneoBio, Telix Pharmaceuticals, Theragnostics, Ratio, Convergent; Financial Interests, Personal, Other, Travel expenses: Bayer, Johnson & Johnson, Sanofi, AstraZeneca, Progenics; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Stocks or ownership: Lilly, GSK, AbbVie, Cardinal Health, United Health Group, PSMA Therapeutics, Clarity Pharmaceuticals, Noria Therapeutics, Clovis Oncology; Financial Interests, Institutional, Research Funding: Bayer, Sanofi, Endocyte, Merck, InVitae, Advanced Accelerator Applications, AstraZeneca, Dendreon, SOTIO, Janssen, Progenics. J. Meltzer, F. Verholen, A. Schmall: Financial Interests, Personal, Other, Employee: Bayer. F. Saad: Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, BMS, Janssen, Merck, Myovant, Novartis, Pfizer, Sanofi; Financial Interests, Personal, Advisory Role: Astellas, AstraZeneca, Janssen, Merck, Myovant, Novartis, Pfizer, Sanofi; Financial Interests, Personal, Other, Honoraria: Astellas, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Sanofi; Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Myovant, Novartis, Pfizer; Non-Financial Interests, Institutional, Other, Local PI nonfinancial interests: Amgen; Financial Interests, Institutional, Other, Local PI nonfinancial interests: Astellas, Bayer, BMS, Janssen, Novartis, Pfizer, Merck, AstraZeneca, Sanofi.