Joan Carles, MD
Researchers are starting to understand which patients with castration-resistant prostate cancer (CRPC) may benefit most from treatment with radium-223 (Xofigo).
Baseline ECOG performance status, alkaline phosphatase (ALP) and hemoglobin (Hb) levels, and the concomitant use of abiraterone acetate (Zytiga) or denosumab were indicators for improved overall survival (OS) with radium-223, according to findings from a phase IIIb follow-up to the pivotal phase III ALSYMPCA trial presented at the 7th European Multidisciplinary Meeting on Urological Cancers (EMUC).
“Data from the posthoc analysis revealing improved OS in patients treated with radium-223 and concomitant denosumab or abiraterone are preliminary but warrant further investigation,” Joan Carles, MD, Val d’Hebron Hospital, Barcelona, Spain, an investigator on the phase IIIb study, said in a presentation at EMUC.
The international, prospective, double-blind, randomized ALSYMPCA trial was the basis of the FDA’s 2013 approval of radium-223 in CRPC. The study enrolled 921 patients with CRPC and ≥2 symptomatic skeletal—but no known visceral—metastases who were unfit for or progressed on docetaxel.
Patients were randomized in a 2:1 ratio to receive 1 to 6 injections of radium-223 at 50 KBq/kg plus best standard of care (BSC) or placebo/BSC. The primary endpoint was OS; secondary endpoints included time to first symptomatic specific skeletal event (SSE), safety, and quality of life (QoL), according to the Functional Assessment of Cancer Therapy–Prostate (FACT-P) scale.
Median OS was 14.9 versus 11.3 months for radium-223 versus placebo, respectively (HR, 0.70; 95% CI, 0.58-0.83; P
<.001). Time to first SSE was 15.6 months with radium-223 versus 9.8 months with placebo (HR, 0.66; 95% CI, 0.52-0.83; P
QoL also favored radium-223, with FACT-P summary scores increasing from baseline by 25% over 16% with placebo. FACT-P total scores at week 42 were -7 versus -12 in patients receiving radium-233 versus placebo, respectively.
The phase IIIb internal extended access trial (iEAP) presented at EMUC confirmed the ALSYMPCA radium-223 data, according to Carles. The iEAP had a similar design as ALSYMPCA, except it was an open-label study and both symptomatic and asymptomatic patients were enrolled.
The iEAP enrolled 839 patients with CRPC and ≥2 bone metastases and followed them for 6 months following treatment. Of the enrolled patients, data from 486 (70%) were censored; median OS in 210 (30%) radium-223–treated patients was 16 months and median time to first SSE was 18 months.
Confirmed median ALP levels ≥50% were observed in 135 (27%) versus 165 (24%), and a confirmed median decrease of ≥50% in PSA levels was seen in 38 (8%) versus 57 (8%) of ALSYMPCA and iEAP patients, respectively.
In the iEAP, OS according to ECOG PS 0, 1, or 2 was not available (NA), 13, and 7 months, respectively (P
OS in patients with ALP ULN (P <.0001). Patients with baseline Hb levels <10 g/L demonstrated OS of 10 months versus 17 months in patients with Hb baseline levels ≥10 (P <.0001).
Patients (n = 156; 121 censored) receiving concomitant abiraterone at baseline achieved OS of NA (95% CI, 16-NA) versus 14 (95% CI, 12-16) months in 540 (censored 365) patients not receiving abiraterone (P <.0001).
Median OS in 138 (103 censored) patients receiving concomitant denosumab was increased to NA (95% CI, 15-NA) versus 13 months (95% CI, 12-NA) in 558 (383 censored) patients not receiving denosumab (P = .009).
“Radium-223 was generally well-tolerated in the iEAP and no new safety concerns were raised,” Carles said.
Treatment emergent adverse events were similar between the two trials, with the most commonly reported being anemia, bone pain, and nausea, which occurred in 31% versus 20%, 50% versus 15%, and 36% versus 11%, of patients in the ALSYMCA and iEAP trials, respectively.
Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213-223.
Saad F, Carles J, Gillessen S, et al. Radium-223 in an international early access program (EAP): effects of concomitant medication on overall survival in metastatic castration-resistant prostate cancer (mCRCP) patients. J Clin Oncol 33, 2015 (suppl; abstr 5034).