770P - Reasons for patients (Pts) discontinuing study treatment (Tx) in the phase 3 ALSYMPCA trial of radium-223 dichloride (Ra-223) in castration-resista...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Supportive Care
Prostate Cancer
Presenter John Logue
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors J. Logue1, S. Wedel2, A. Chodacki3, O. Sartor4, S. Nilsson5, R.E. Coleman6, N. James7, A. Aksnes8, M. Wahba9, C. Parker10
  • 1Urology, Christie Hospital, M20 4BX - Manchester/GB
  • 2Klinik Für Urologie Und Kinderurologie, Ortenau Klinikum Offenburg Gengenbach, Offenburg/DE
  • 3Nuclear Medicine, Hospital Kochova, Chomutov/CZ
  • 4Department Of Medicine: Section Of Hematology & Medical Oncology And Department Of Urology, Tulane Cancer Center, 70112 - New Orleans/US
  • 5Clinical Oncology, Karolinska University Hosiptal, 171 76 - Stockholm/SE
  • 6Academic Unit Of Clinical Oncology, Weston Park Hospital, Sheffield/GB
  • 7Cancer Research Unit, University of Warwick, Coventry, and University Hospitals, Birmingham NHS Trust, CV4 7AL - Coventry/GB
  • 8Clinical Research, Algeta ASA (Bayer), Oslo/NO
  • 9Us Medical Affairs, Bayer HealthCare, Whippany/US
  • 10Academic Urology, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton/GB

Abstract

Aim

Adherence to prescribed tx is an important factor in determining outcome in advanced CRPC pts, and is often driven by drug tolerability. In ALSYMPCA, the first-in-class α-emitter Ra-223 had a highly favorable safety profile and was well tolerated (Parker et al. NEJM 2013). Here we report results from a post hoc analysis identifying factors associated with ALSYMPCA study tx discontinuation to inform pt management and allow the full course of Ra-223 therapy.

Methods

ALSYMPCA pts had progressive, symptomatic CRPC with ≥ 2 bone mets, had no known visceral mets, and had received docetaxel or were unfit for or declined docetaxel. Pts were randomized 2:1 to 6 injections (inj) of Ra-223 (50 kBq/kg IV) q 4 wk or matching placebo (pbo). Pts who did not receive all 6 study inj were considered to have discontinued tx and withdrawn early from the study. A post hoc analysis of these pts was performed.

Results

Of the 921 pts enrolled, 901 were treated (Ra-223, n = 600; pbo, n = 301); 209 (35%) Ra-223 and 157 (52%) pbo pts discontinued tx after inj 1-5. Prior vs no prior docetaxel was associated with a greater percentage of pts discontinuing tx in both groups. Adverse events (AEs) were the primary reason for discontinuing tx across all categories (Table on following page). The most common AE was disease progression (Ra-223, 17%; pbo, 16%). Anemia was a more common reason for discontinuing Ra-223 (15% vs 3%), as was general physical health deterioration (9% vs 2%); bone pain was more common with pbo (11% vs 2%), as was fatigue (8% vs 4%).

Pts (n) Discontinuing Treatment After Injections 1-5
Pt Group Total Discontinued Reason for Discontinuing Treatment Total, n (%) RA N = 600 Total, n (%) Pbo N = 301 Ra Inj 1 Pbo Inj 1 Ra Inj 2 Pbo Inj 2 Ra Inj 3 Pbo Inj 3 Ra Inj 4 Pbo Inj 4 Ra Inj 5 Pbo Inj 5
All pts 209 (35) 157 (52) 18 21 37 36 48 37 60 34 46 29
AE 92 (44) 59 (38) 7 11 14 12 23 10 27 16 21 10
Death 27 (13) 28 (18) 6 4 5 3 7 8 4 5 4 8
Inv Request 25 (12) 27 (17) 1 0 7 6 3 9 9 7 5 5
Pt Request 40 (19) 22 (14) 4 4 7 6 9 4 8 3 12 5
Other 26 (12) 21 (13) 0 2 4 9 6 6 12 3 4 1
Prior Doce 132 (22) 92 (30) 11 12 17 21 31 20 40 20 33 19
AE 60 (45) 37 (40) 3 8 6 6 13 5 22 11 16 7
Death 12 (9) 12 (13) 5 2 1 2 4 4 1 1 1 3
Inv Request 17 (13) 18 (20) 1 0 5 5 2 4 5 5 4 4
Pt Request 29 (22) 15 (16) 2 1 3 3 7 3 7 3 10 5
Other 14 (11) 10 (12) 0 1 2 5 5 4 5 0 2 0
No Prior Doce 77 (13) 65 (21) 7 9 20 15 17 17 20 14 13 10
AE 32 (42) 22 (35) 4 3 8 6 10 5 5 5 5 3
Death 15 (19) 16 (25) 1 2 4 1 3 4 3 4 3 5
Inv Request 8 (10) 9 (14) 0 0 2 1 1 5 4 2 1 1
Pt Request 11 (14) 7 (11) 2 3 4 3 2 1 1 0 2 0
Other 12 (16) 11 (17) 0 1 2 4 1 2 7 3 2 1

Conclusions

The percentage of pts discontinuing tx before the full course of therapy was smaller with Ra-223 than with pbo, which indicates a positive tx effect and safety profile. Supportive measures to improve the pts' general health and tx of anemia could help achieve the full course of Ra-223 therapy.

Disclosure

O. Sartor: has had a consultant or advisory relationship with and has received research funding from Algeta and Bayer; S. Nilsson: has had a consultant or advisory relationship with Algeta and has received remuneration from Bayer for travel costs and accommodations for study and writing meetings;

R.E. Coleman: has had a consultant or advisory relationship with Bayer, has received honoraria from Bayer and Amgen, and has provided expert testimony for Novartis; N. James: has had a consultant or advisory relationship with Algeta and Bayer; A. Aksnes: is employed by Algeta ASA (Bayer); M. Wahba: is employed by Bayer HealthCare; C. Parker: has had a consultant or advisory relationship with Algeta, Bayer, and BNIT, and has received honoraria from Amgen, Astellas, Bayer, Janssen, Sanofi-Aventis, and Takeda. All other authors have declared no conflicts of interest.