936P - Safety of cytotoxic chemotherapy following radium-223 chloride (RA-223) therapy in the phase 3 ALSYMPCA study in patients with castration-resistant...
|Date||29 September 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation I|
|Topics|| Supportive Care
O. Sartor1, R.E. Coleman2, S. Nilsson3, N. Vogelzang4, A. Cross5, C.G. O'Bryan-Tear6, K. Staudacher6, J.E. Garcia-Vargas7, J. Zou8, C. Parker9
Ra-223 is a first-in-class alpha-emitter pharmaceutical that targets bone metastases with high-energy, extremely short range (<100 µm) alpha-particles. ALSYMPCA compared efficacy and safety of Ra-223 vs placebo (Pbo) in CRPC patients (pts) with bone metastases receiving best standard of care. In the updated analysis of all 921 randomized pts (Ra-223, 614; Pbo, 307) prior to Pbo crossover, the median overall survival (OS) benefit for Ra-223 was 3.6 months (hazard ratio 0.695) and the incidence of myelosuppression was low. The use of cytotoxic chemotherapy (Chemo) after completion of study treatment was evaluated.Methods
The cohort for this analysis consisted of all pts who received Chemo after completion of Ra-223 or Pbo. Chemo agents were identified, and length of time from last injection of study drug to start of Chemo and its duration calculated. Available hematology data were reviewed, and post hoc analysis of survival conducted.Results
The proportion of pts receiving subsequent Chemo was 90/614 (15%) in the Ra-223 group and 54/307 (18%) in the Pbo group. Docetaxel (n = 102), mitoxantrone (n = 23), and cyclophosphamide (n = 19) were the most commonly used. Duration of Chemo and available docetaxel dosage data were similar in both groups. Median time to Chemo was 2 weeks longer following Ra-223. Median OS from start of Chemo was 15.6 mos and 14.6 mos in the Ra-223 and Pbo groups, respectively (P = .6930). Number of deaths and causality during and 30 days post Chemo and limited available hematologic data were similar in both groups (Table).Conclusions
Patients were able to receive Chemo following Ra-223 and have a similar safety profile and outcome as for Chemo following Pbo. No toxic deaths occurred. Prospective studies to evaluate Chemo following Ra-223 are warranted.
|Parameter||Ra-223 + BSC (n = 90)||Placebo + BSC (n = 54)|
|Median time to Chemo; days (range)||79.0 (2–667)||64.5 (2–448)|
|Median duration Chemo; days (range)||117.5 (1–809)||112.5 (1–863)|
|Chemo = docetaxel; n (%)||63 (70.0)||39 (72.2)|
|Docetaxel daily dose (mg); n||22||17|
|Mean (SD)||97.8 (41.6)||102.7 (46.3)|
|Median (min-max)||92.5 (35-150)||120.0 (30-165)|
|Deaths on Chemo; n (%)||13 (14.4)||8 (14.8)|
|Cause: PC and skeletal mets (± other mets)||9 (10.0)||7 (13.0)|
|PC with other mets (or mets not specified)||3 (3.3)||0 (0)|
|Cerebral hemorrhage due to trauma Cardiopulmonary failure||1 (1.1) 0 (0)||0 (0) 1 (1.1)|
|Deaths within 30 days post Chemo; n (%)||5 (5.6)||2 (3.7)|
|Cause: PC and skeletal mets (± other mets)||3 (3.3)||2 (3.7)|
|Bronchopneumonia Respiratory failure + pulmonary edema||1 (1.1) 1 (1.1)||0 (0) 0 (0)|
|Neutrophils; (Absolute) (x10^9/L) Baseline, n Median (min-max) Month 2, n Median (min-max) Month 4, n Median (min-max) Month 6, n Median (min-max) Month 8, n Median (min-max) Month 10, n Median (min-max) Month 12, n Median (min-max)||88 3.6 (0.9-26.0) 47 4.4 (0.5-24.4) 41 3.8 (1.3-10.8) 23 3.5 (0.5-6.3) 12 3.5 (1.9-9.4) 13 3.6 (1.1-8.9) 8 5.0 (2.5-7.1)||49 4.6 (1.9-16.4) 30 5.7 (1.6-13.1) 19 4.6 (1.1-8.9) 12 4.7 (1.5-12.2) 7 3.9 (3.0-6.4) 8 4.6 (3.0-8.5) 6 5.6 (2.8-8.9)|
BSC, best standard of care; Chemo, cytotoxic chemotherapy; mets, metastases; PC, prostate cancerDisclosure
O. Sartor: O. Sartor has served in a consultant or advisory role for Algeta ASA and Bayer.
S. Nilsson: S. Nilsson has served in a consultant or advisory role for Algeta ASA.
N. Vogelzang: N. Vogelzang has served in a consultant or advisory role for and has received grant/research support from Algeta ASA and Bayer.
C.G. O'Bryan-Tear: C.G. O'Bryan-Tear is employed by and has an ownership interest in Algeta ASA.
K. Staudacher: K. Staudacher is employed by and has an ownership interest in Algeta ASA.
J.E. Garcia-Vargas: J. Garcia-Vargas is employed by Bayer HealthCare Pharmaceuticals.
J. Zou: J. Zou is employed by Bayer HealthCare Pharmaceuticals.
C. Parker: C. Parker has served in a consultant or advisory role for Algeta ASA (uncompensated) and Bayer.
All other authors have declared no conflicts of interest.