Effects of denosumab versus zoledronic acid (ZA) on health-related quality of life (HRQL) in metastatic breast cancer: Results from a randomized phase III trial.

Abstract

1025 Background: Bone metastases in patients (pts) with breast cancer can lead to skeletal related events (SREs), pain, and decreased HRQL. Denosumab, an investigative fully human monoclonal antibody against RANKL, was previously shown to be superior in delaying SREs and more effective in delaying moderate or severe pain in pts with advanced breast cancer compared with ZA. Here, we assess HRQL in this head-to-head study of metastatic breast cancer pts. Methods: Eligible pts received subcutaneous (SC) denosumab 120 mg or intravenous (IV) ZA 4 mg every 4 weeks in a double-blind, double-dummy fashion. Pts completed Functional Assessment of Cancer Therapy-General (FACT-G) questionnaires at baseline (BL), day 8, and before each monthly visit to assess overall HRQL. Higher scores (range 0–108) represent better HRQL. Improvement, maintenance, and worsening of HRQL were assessed through week 73, when 30% of pts had dropped out due to death, disease progression, or consent withdrawn. Results: BL mean FACT-G total score was 72.7 (SD 16.4) for denosumab (n=956) and 73.6 (SD 16.5) for ZA (n=952). Mean scores improved from BL through week 73 in both groups. From week 5–73, an average of 3.2% (range 1%–7%) more denosumab- treated pts experienced clinically meaningful improvement in HRQL (≥ 5-point increase in FACT-G total score) than ZA-treated pts. At week 25, 37.1% of denosumab vs. 31.4% of ZA pts experienced improvement (p=0.017). In addition, a lower proportion of denosumab pts experienced worsening in HRQL compared with ZA pts (Table). Conclusions: In bone metastases secondary to breast cancer, pts receiving denosumab or ZA showed improvement or maintenance in HRQL relative to BL, while a greater proportion of denosumab-treated pts reported a clinically meaningful improvement in HRQL. Potential benefits of SC delivery of denosumab on HRQL were not captured since both treatment arms received SC and IV administration. % of denosumab (n=787)+ and ZA (n=768)= pts reporting ≥5-point change between BL and week 25 Week 25 FACT-G total score ≥5 point improvement No change ≥5 point worsening Denosumab 37.1%* 30.2% 32.7% ZA 31.4%* 33.9% 34.8% + Pts with both BL and week 25 data . * p value < 0.02. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Ameen, Amgen, Novartis Amgen Amgen, Novartis Amgen, Novartis Novartis