CHICAGO, IL USA (UroToday.com) - Radium-223 dichloride (Ra-223), a first-in-class alpha-emitting radiopharmaceutical, was associated with meaningful pain relief for patients with castrate-resistant prostate cancer (CRPC) and symptomatic bone metastases.
In results from a multi-institutional study presented at the 2015 ASCO Annual Meeting, 42% of mCRPC patients reported improved pain during Ra-223 treatment for mCRPC, defined as a decrease in 2 or more points in the Brief Pain Inventory (BPI-SF) questionnaire. The data were derived from U.S. Ra-223 early access program (EAP).
The U.S. EAP was a phase 2 prospective, interventional, open-label, multicenter study conducted in the United States to provide early access to Ra-223 patients with CRPC and symptomatic bone metastases prior to regulatory approval, and as a mechanism to monitor Ra-223 short and long-term safety.
In this analysis, pain severity assessments were based on the ‘worst pain’ item from the BPI-SF. Eligible patients were not receiving opioids at baseline. Hypothesis tests were based on pain changes from baseline. The investigators, led by Christopher Sweeney of the Dana-Farber Cancer Institute, defined “meaningful” as a change in BPI-SF scores of 2 or more points from baseline. Pain levels were assessed at baseline, during treatment, and at a follow-of up to 6 months after a last treatment visit.
Of 182 Ra-223-treated patients with pain scores at baseline, 109 were not receiving opioids. Of these patients, 6% had a score of 0 (no pain); 46% reported scores indicating mild pain; 34% had moderate pain; and 14% reported severe pain at the baseline assessment.
Among these 109 patients, 42% had improved pain—a decrease in BPI-SF scores of 2 or more without worsening; 18% had stable pain or no change equivalent to 2 or more points. Twenty-eight percent of subjects had worsening pain—an increase of 2 or more points or initiation of opioids—and never had improvement in pain. Ten percent of subjects experienced both improvements and worsening of pain at different times during treatment with Ra-223. (post-treatment data were not available for 2% of patients.)
Post-baseline data for 107 patients revealed a significant decrease in mean pain severity from baseline (P < 0.5) at all treatment visits/assessments. Among the assessable 107 patients who could have had pain improvement of 2 or greater in BPI-SF scores, 59% experienced reduced pain during at least one medical visit while on Ra-223 therapy.
These results, while demonstrating meaningful pain relief for mCRPC patients with bone metastasis receiving Ra-223, also included what the investigators believe is a confounding effect from change in opioids after initiation of Ra-223 therapy.
The data builds upon a prior foundation of evidence for pain relief with Ra-223.
- Ra-223 significantly prolonged time to first opioid use (HR=0.62; P=0.002), and
- time to first external beam radiation therapy (EBRT) for bone pain (HR=0.67; P=0.00) in the phase III ALSYMPCA trial, as well as in two previous phase II trials.
This feature of Ra-223 is intrinsic to its mechanism of action of a bone-seeking nucleotide. “When injected intravenously, radium-223 has the ability to behave like calcium, and will be attracted to the bone, in particular to areas of damage to the bone” explained Joe O’Sullivan, MD, from Queens University, Belfast, who was not involved in this study, but was a co-investigator on the European EAP. The drug then delivers its therapy by ionizing radiation in the form of an alpha particle, a type of ionizing radiation that damages DNA.
Sweeney C, Sartor AO, Vogelzang NJ, et al. Effect of radium dichloride (Ra-223) on pain from US EAP. Abstract e16086. 2015 ASCO Annual Meeting.
Presented by Christopher Sweeney, MBBS at the American Society of Clinical Oncology (ASCO) Annual Meeting - Illumination & Innovation: Transforming Data into Learning - May 29 - June 2, 2015 - Chicago, Illinois USA
Dana-Farber Cancer Institute, Boston, MA USA