Pain Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with 223Ra: PARABO, a Prospective, Noninterventional Study

Abstract

²²³Ra, a targeted α-therapy, is approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have bone metastases. In the phase 3 ALSYMPCA study, ²²³Ra prolonged survival and improved quality of life versus placebo. Our real-world study, PARABO, investigated pain and bone pain-related quality of life in patients with mCRPC and symptomatic bone metastases receiving ²²³Ra in clinical practice. Methods: PARABO was a prospective, observational, noninterventional single-arm study conducted in nuclear medicine centers across Germany (NCT02398526). The primary endpoint was a clinically meaningful pain response (≥2-point improvement from baseline for the worst-pain item score in the Brief Pain Inventory-Short Form). Results: The analysis included 354 patients, who received a median of 6 ²²³Ra injections (range, 1-6). Sixty-seven percent (236/354) received 5-6 injections, and 33% (118/354) received 1-4 injections. Of 216 patients with a baseline worst-pain score of more than 1, 59% (128) had a clinically meaningful pain response during treatment. Corresponding rates were 67% (range, 98/146) with 5-6 ²²³Ra injections versus 43% (range, 30/70) with 1-4 injections, 60% (range, 60/100) in patients with no more than 20 lesions versus 59% (range, 65/111) in those with more than 20 lesions, and 65% (range, 69/106) in patients without prior or concomitant opioid use versus 54% (range, 59/110) in those with prior or concomitant opioid use. Mean subscale scores (pain severity and pain interference) on the Brief Pain Inventory-Short Form improved during treatment. Conclusion: ²²³Ra reduced pain in patients with mCRPC and symptomatic bone metastases, particularly in patients who received 5-6 injections. The extent of metastatic disease did not impact pain response.

Keywords: 223Ra; bone metastases; castration-resistant prostate cancer; pain response; targeted α-therapy.

FIGURE 1.

Rates of clinically meaningful pain response. Responses were evaluated in patients with baseline Brief Pain Inventory–Short Form worst-pain item score > 1 (n = 216), with data also stratified by number of ²²³Ra injections, disease extent, and prior or concomitant opioid use.

FIGURE 2.

Changes in pain over time. Treatment visits correspond to ²²³Ra injections. Shown are mean change in mean Brief Pain Inventory–Short Form scores from baseline (full analysis set; 274/354 patients completed Brief Pain Inventory–Short Form questionnaire and were included). BPI-SF = Brief Pain Inventory–Short Form.

FIGURE 3.

Changes in proportion of patients with complete or nearly complete pain relief and bone pain–related QoL over time. Treatment visits correspond to ²²³Ra injections. (A) Proportion of patients with 80%−100% pain relief. (B) Mean change from baseline on scores for Functional Assessment of Cancer Therapy Quality-of-Life Measurement in Patients with Bone Pain. FACT-BP = Functional Assessment of Cancer Therapy Quality-of-Life Measurement in Patients with Bone Pain.

FIGURE 4.

Areas that hurt most at baseline and at follow-up after end of treatment. Numbers indicate percentage of patients (≥10%) who reported areas that hurt most at baseline and end of treatment (in same areas as baseline). Patients may have reported pain in more than one area. Circles indicate pelvis (left and right), thigh (left and right), thoracic vertebrae, and lumbar vertebrae. Circle sizes represent percentage of patients who reported that area; 10% reference scale is shown.

FIGURE 5.

OS: full analysis set (n = 354).

FIGURE 6.

Incidence of new symptomatic skeletal events (full analysis set). EBRT = external-beam radiation therapy.