Abstract 1998
Background
Radium-223 (Ra-223) 50 kBq/kg IV (55 kBq/kg after NIST update) every 4 wk × 6 injections (inj) is indicated in symptomatic bone-metastatic castration-resistant prostate cancer (mCRPC) patients (pts) with no visceral metastases (mets). In an international prospective trial in mCRPC pts (NCT01934790), Ra-223 re-treatment (re-tx) after initial 6 inj was well tolerated, with very low radiologic bone progression rates (Sartor. ASCO GU 2016). Reported are safety and total alkaline phosphatase (ALP) and prostate-specific antigen (PSA) dynamics.
Methods
All pts had CRPC with bone mets and completed 6 Ra-223 inj with no bone progression during that initial tx. Pts had radiologic or clinical progression after initial Ra-223 tx, and adequate hematologic (heme) values. Pts who started subsequent anticancer tx must have progressed on the last anticancer tx. Concomitant agents (except cytotoxic) were allowed at investigator discretion. Addition of abiraterone and enzalutamide was not allowed during Ra-223 re-tx. Primary end point was safety; exploratory efficacy end points included times to ALP and PSA progression, and ALP and PSA response rates (≥30% decline from baseline).
| Re-tx Study, N = 44 | Re-tx Study, N = 44 | Re-tx Study, N = 44 | ALSYMPCA Ra-223 Arm, N = 600 | ALSYMPCA Ra-223 Arm, N = 600 | ALSYMPCA Ra-223 Arm, N = 600 | |
|---|---|---|---|---|---|---|
| Treatment-emergent adverse events* | All Gr | Gr 3 | Gr 4 | All Gr | Gr 3 | Gr 4 |
| ≥1 TEAE, %† | 93 | 41 | 7 | 93 | 35 | 9 |
| Heme, % | ||||||
| Anemia | 14 | 5 | 0 | 31 | 11 | 2 |
| Thrombocytopenia | 2 | 2 | 0 | 12 | 3 | 3 |
| Neutropenia | 0 | 0 | 0 | 5 | 2 | 1 |
| Leukopenia | 2 | 0 | 0 | 4 | 1 | 20% pts §ALSYMPCA intent-to-treat population ‖n/N = pts with response/pts with valid lab assessment ¶For ALSYMPCA, ALP response: ≥ 30% decline from baseline confirmed by a second measurement ≥4 wk later; PSA response: ≥ 30% decline from baseline # ALSYMPCA: End of tx (4 wks after last inj) **N = safety population; pts with no valid postbaseline lab assessment counted as nonresponders; database cutoff date was June 11, 2015 NA = not applicable
ResultsOf 44 Ra-223 re-tx pts, 29 (66%) received all 6 inj. Median time from last inj of initial Ra-223 tx was 6 mo. There were no marked alterations in tx-emergent adverse event (TEAE) incidence vs ALSYMPCA (Table) and no grade 4 or 5 heme TEAEs; 3 (7%) re-tx pts had grade 3 or 4 tx-related TEAEs. Maximum follow-up times for ALP and PSA progression were 12.8 and 11.4 mo, respectively. Median time to ALP progression was not reached. Median time to PSA progression was 2 mo. ALP and PSA response rates at wk 12, 24, and any time before database cutoff are reported (Table). ALP, PSA, and heme lab values will be reported. ConclusionsRa-223 re-tx was well tolerated, with minimal heme toxicity and ALP and PSA profiles similar to those of ALSYMPCA. Clinical trial identificationNCT01934790 Legal entity responsible for the studyPharmaceuticals Division of Bayer FundingPharmaceuticals Division of Bayer DisclosureO. Sartor: Consultant or advisory role for Astellas, Bavarian Nordic, Bayer, Bellicum, Biscayne, Johnson & Johnson, Medivation, Oncogenex, Sanofi, Algeta, Aragon, and Pfizer; research funding from Bayer, Johnson & Johnson, Progenics, Sanofi, Algeta, and Takeda. D. Heinrich: Honoraria from and consultant or advisor for Bayer, Johnson & Johnson, and Astellas; research funding from Bayer, Johnson & Johnson, BMS, and Aragon Pharmaceuticals. N. Mariados: Stock or ownership interest in and travel, accommodations, expenses from Augmenix; honoraria from and speakers bureau for Bayer. M.J. Méndez Vidal: Consulting or advisory role for Janssen-Cilag, Pfizer, Astellas, GlaxoSmithKline, Sanofi, and Bayer; travel, accommodations, expenses from Janssen-Cilag, Pfizer, Astellas, and GlaxoSmithKline. D. Keizman: Consulting or advisory role for, honoraria from, and travel, accommodations, and expenses from Bayer, Pfizer, Sanofi, and Janssen Oncology. C. Thellenberg Karlsson: Consulting or advisory role for Bayer and Sanofi. G. Procopio: Consulting or advisory role for Janssen, Novartis, and Bayer; honoraria from Astellas and Janssen. S. Severi: Speakers bureau for Bayer. V. Wagner: Was employed by Merck; is now employed by Bayer; stock or other ownership in Bayer, Merck, and Amgen. J. Garcia-Vargas: Employed by Bayer; travel, accommodations, expenses from Bayer. R. Li: Employed by Bayer. All other authors have declared no conflicts of interest. Resources from the same session2826 - A multicenter phase II study of preoperative concurrent chemoradiotherapy with S-1 plus irinotecan for locally advanced rectal cancer: SAMRAI-2Presenter: Masafumi Noda Session: Poster Display Resources: Abstract 3036 - Temozolimide and capecitabine in patients with refractory KRAS wildtype metastatic colorectal cancer. 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