22120 Background: In patients (pts) with advanced cancer, bone metastases (mets) are the most common source of chronic cancer-related pain. Pts with untreated bone mets typically have pain clustered with fatigue, increased use of analgesics, and a reduced sense of overall well-being; however, residual pain despite treatment can be viewed as an independent outcome. Pain scores may therefore provide prognostic insight into risks of skeletal-related events (SREs) and death in these pts. To evaluate this, we conducted a retrospective analysis in 2 large zoledronic acid (ZOL) clinical trials in pts with bone mets from breast cancer (BC) or prostate cancer (PC). Methods: Pts treated with ZOL who had BC (n = 664 at baseline) or PC (n = 376 at baseline) and complete pain, lesion site, lesion #, and SRE history data for the respective time points were included. At baseline and 6 and 12 mo, pts were categorized by their Brief Pain Inventory (BPI; 1 to 10 scale) as group A (< 2.5), group B (2.5 to 5.0), group C (5.0 to 7.5), and group D (≥ 7.5). Univariate analyses were performed for relative risks of first SRE and death for each group vs group A. Results: Group D contained <10% of pts at each time point, and is not reported herein. For BC, many pts transitioned from higher-pain to lower-pain groups during treatment, whereas pain was persistent among PC pts. For BC, at each time point groups B and C had ∼2-fold increased risks of first SRE vs group A (P < .05 for all). Groups B and C consistently had increased risks of death vs group A at each time point, although the magnitude and significance of the differences varied throughout the study. For PC, Group B and C had increased risks of death and first SRE, respectively, vs group A at baseline (P < .003 for each). During therapy (6 and 12 mo), group C had ∼2-fold increased risks of first SRE and death vs group A, and group B also had ∼2- fold increased risk of first SRE vs group A (P < .02 for both 6 and 12 mo), but correlations with overall survival were inconsistent. Conclusions: These analyses suggest that the time course of pain levels may provide important prognostic information during ZOL therapy in pts with bone mets from BC or PC. Therefore, residual pain level may not only be an indicator to increase palliative care but should also play a role in evaluating overall treatment options. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Pharmaceuticals Corporation Novartis Pharmaceuticals Inc. Novartis Pharmaceuticals Inc. Novartis Pharmaceuticals Inc.