Abstract 639P
Background
223Ra is indicated for mCRPC pts with symptomatic bone metastases, while limited data exist on its impact as monotherapy in asymptomatic pts. Androgen Receptor splice Variant 7 (AR-V7) is a negative prognostic/predictive marker for response to new hormonal treatments but its correlation with 223Ra is lacking. Study aim was to assess the activity and safety of 223Ra in mCRPC pts and the association of AR-V7 status with 223Ra efficacy.
Methods
This single-arm, phase 2 trial enrolled asymptomatic mCRPC pts with bone metastases and no visceral involvement. Pts who have progressed to ≥24 weeks (w) of 1st line abiraterone acetate or enzalutamide received 223Ra (55 kBq/kg) every 4w for 6 cycles. Primary endpoint was radiographic progression-free survival (rPFS) as per PCWG2 criteria. Secondary endpoints included rPFS according to circulating tumor cell AR-V7 status, overall survival (OS), time to first symptomatic skeletal event (SSE), time to prostate-specific antigen (PSA) progression, PSA response (≥30% at 12w), and safety.
Results
Between 12/2016 and 11/2018, 52 pts were enrolled from 9 sites in Spain. Median (m) age was 76 years (range 51–89) and mPSA 20.3 μg/L (0.04–703.3). Bone lesions were <6, 6–20, >20 in 28.8%, 69.2%, and 1.9% of pts, respectively. 94.2% of pts had ≥2 prior any hormone therapies and 7.7% had received docetaxel in the hormonosensitive setting. 9.6% pts were AR-V7+. Median duration of treatment and follow-up were 5.5 and 6.6 months (mo), respectively. Study met primary endpoint with mrPFS of 5.4 mo (95% CI 4–5.5). Results were inconclusive for AR-V7 analysis (p=0.118). OS data were immature (14 deaths, 26.9%). SSE events were reported in 9.6% of pts. Median time to PSA progression was 3.6 mo. PSA responders were 15.4%. 65.4% of pts received 5/6 treatment cycles. Grade (G)3/4 adverse events (AEs) were reported in 25% of pts. Most frequent G3/4 AEs were anemia (11.5%) and thrombocytopenia (5.8%). 3.8% of pts discontinued 223Ra due to AEs. No therapy-related deaths occurred.
Conclusions
223Ra is active and safe for 2nd line treatment in asymptomatic mCRPC pts with bone metastases who have progressed to 1st line new hormonal regimens.
Clinical trial identification
NCT03002220.
Editorial acknowledgement
Legal entity responsible for the study
MedSIR.
Funding
Bayer.
Disclosure
J. Carles: Advisory/Consultancy: Bayer, Johnson & Johnson, Bristol-Myers Squibb, Astellas Pharma, Pfizer, Sanofi, MSD Oncology, Roche, AstraZeneca; Speaker Bureau/Expert testimony: Bayer, Johnson & Johnson, Asofarma, Astellas Pharma; Travel/Accommodation/Expenses: BMS, Ipsen, Roche, AstraZeneca; Research grant/Funding (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Intern. M.J. Mendez Vidal: Honoraria (self): Astellas Pharma, Roche, BMS, Ipsen; Advisory/Consultancy: Janssen-Cilag, Pfizer, Astellas Pharma, Sanofi, Bayer, BMS, Novartis, Roche, Ipsen, EUSA Pharma; Travel/Accommodation/Expenses: Janssen-Cilag, Pfizer, Astellas Pharma, BMS, Roche. S. Vazquez Estevez: Advisory/Consultancy: Pfizer, Astellas, Janssen, MSD, Bayer, Roche, BMS, Boehringer, AstraZeneca, Ipsen, Novartis, Eusa Pharma, Eisa and Sanofi; Speaker Bureau/Expert testimony: Lilly, Astellas, Bayer, Roche, Boehringer, Ipsen, Novartis, AstraZeneca and Sanofi; Travel/Accommodation/Expenses: Pfizer, Roche and AstraZeneca. A. González del Alba: Honoraria (self): Sanofi/Aventis, Roche, Pfizer, Astellas Pharma, Janssen-Cilag, Novartis, Ipsen; Advisory/Consultancy: Astellas Pharma, Sanofi, Bayer, Janssen Oncology, Pfizer, Bristol-Myers Squib,b Eisai, Pierre Fabre, EUSA Pharma, Roche, Novartis, Ipsen, AstraZeneca; Speaker Bureau/Expert testimony: Ipsen, Roche, Pfizer, Pierre Fabre, Janssen-Cilag; Travel/Accommodation/Expenses: Astellas Pharma, Pfizer, Janssen Oncology, Sanofi, Bristol-Myers Squibb, MSD Oncology, Roche, Ipsen. J.M. Piulats: Advisory/Consultancy: Roche, Novartis, Jansen, Astellas, Bayer, Sanofy-Genzyme, MSD, BMS, Merk-Serono, Clovis, AstraZeneca, Beigene, VCN biotech; Research grant/Funding (self): Roche, Jansen, Astellas, MSD, BMS, Merk-Serono, AstraZeneca, Beigene, VCN biotech.; Travel/Accommodation/Expenses: Roche, Astellas, Jansen. P. Borrega García: Advisory/Consultancy: Sanofi, Roche; Advisory/Consultancy: BAYER; Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Ipsen. E. Gallardo: Advisory/Consultancy: Sanofi, Janssen, Astellas, Pfizer, Bayer, Roche, Ipsen, Novartis, Eisai, EUSA Pharma, BMS, AstraZeneca, Merck, Rovi, Daiichi Sankyo, Techdow; Speaker Bureau/Expert testimony: Astellas, Janssen, Sanofi, Bayer, Ipsen, Pfizer, Roche, BMS, Novartis, Rovi, Daiichi Sankyo, Leo Pharma, Menarini, Eisai, MSD, Boehringer Ingelheim, Merck; Research grant/Funding (institution): Astellas, Janssen, Sanofi, Pfizer, Bayer, Ipsen, Roche, Ferrer, GSK, BMS; Travel/Accommodation/Expenses: Astellas, Janssen, Sanofi, Bayer, Ipsen, Roche, Novartis, Pierre Fabre, Pfizer, Eisai. R. Morales Barrera: Advisory/Consultancy: Sanofi Aventis, Bayer, Janssen, AstraZeneca, Merck Sharp & Dohme, Asofarma.; Travel/Accommodation/Expenses: Roche, Sanofi Aventis, Astellas, Janssen, Merck Sharp & Dohme, Bayer, Pharmacyclics, Clovis Oncology and Lilly. O. Reig: Speaker Bureau/Expert testimony: BMS, Ipsen, Pfizer; Travel/Accommodation/Expenses: Ipsen, Pfizer. C. Garcías de España: Advisory/Consultancy: Bayer, Janssen. C. Suarez: Honoraria (self): Astellas, AstraZeneca, Bayer, BMS, Eusa, Ipsen, Novartis, Pfizer, Sanofi-Aventis, Roche, Merck Sharp & Dohme Corp; Honoraria (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma, AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Intern; Non-remunerated activity/ies: Steering Committee Roche, Steering Committee BMS. All other authors have declared no conflicts of interest.