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Introduction: Use of pegfilgrastim in patients who are at high risk of febrile neutropenia (>18%) results in a 94% reduction in febrile neutropenia. Use of pegfilgrastim is also associated with increased chemotherapy Relative Dose Intensity (RDI) due to fewer dose reductions, delays and discontinuations. Higher RDI has been associated with increased survival. Pegfilgrastim use historically required patients to return the day after chemotherapy. Introduction of the on-body injector (OBI) allows for next day delivery of growth factor without patients having to come back to the clinic. We conducted a study comparing neutropenia rates, dose delays and total cost of care for breast cancer patients receiving chemotherapy with high risk of febrile neutropenia who received (1) no pegfilgrastim, (2) pegfilgrastim via pre-filled syringe (PFS), (3) pegfilgrastim via OBI. Methods: The data utilized for this study originates from the EHRs, practice management systems and CMS claims obtained as part of the Oncology Care Model (OCM) for eight practices supported by Integra Connect Population Health. Using our harmonized data model, DTX, we constructed synthetic chemotherapy episodes of care. Each episode began with an administration of a chemotherapy regimen defined as having a high risk of febrile neutropenia per NCCN. The episode ended the day of the next chemotherapy administration, or after 14 days if no subsequent chemotherapy was given. Each episode was assigned to a cohort, no pegfilgrastim, pegfilgrastim via PFS, or pegfilgrastim via OBI. To evaluate the efficacy and toxicity associated with pegfilgrastim administration, we conducted a matched cohort analysis. Patients were matched based on age, sex, cancer type, number of comorbidities, regimen, chemo start date (within 90 days), whether the administration was the last cycle of chemotherapy, and OCM provider quality metrics. Results: Compared with no pegfilgrastim, PFS episodes had 9.9% less grade IV neutropenia (ANC < 500, p < 0.001) and 5.6% fewer dose delays (p=0.0014, n=916 in each arm). Compared with OBI, PFS episodes had 0.3% less grade IV neutropenia (p=0.47) and 5.3% fewer dose delays (p=0.009, n=2,727 in each arm). Exploratory analysis highlighted differences in physician office and hospital utilization. PFS episodes include more non-chemotherapy office visits than OBI episodes (2.1 vs 1.3, p < 0.001). PFS patients are more likely to have an unplanned office visit (64% vs 23%, p < 0.001) and more likely to receive hydration during an episode (34% vs. 21%, p = 0.021). PFS episodes include less hospital utilization compared with OBI episodes. OBI episodes are 23% more likely to include hospitalization (5.0% vs 6.2%, p=0.031). Discussion: As expected, this observational real-world analysis shows that the use of pegfilgrastim via PFS or OBI is associated with reduced neutropenia rates and reduced dose delays compared with no pegfilgrastim. Comparing PFS with OBI, we see similar neutropenia rates, but PFS shows fewer dose delays and fewer hospitalizations. Exploratory analysis provides some insight into these dose delays and related health care utilization. Our analysis shows that patients returning next day to the cancer center to receive pegfilgrastim frequently receive other services such as labs and hydration. These services lead to fewer dose delays, perhaps because toxicities other than neutropenia are detected earlier in the episode and can be managed in the office. This implies that use of PFS may be used as part of a strategy to shift site of service for management of side effects into the physician office and away from hospitals and emergency departments. Citation Format: Jennifer Webster, Jeffrey Scott, Danielle Wieland, Joseph Donaldson, Ash Malik, Rushir Choksi. Patients receiving pegfilgrastim via prefilled syringe received closer care when compared with on-body injector [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-12.

Increased osteoclastogenesis and angiogenesis occur in physiologic and pathologic conditions. However, it is unclear if or how these processes are linked. To test the hypothesis that osteoclasts stimulate angiogenesis, we modulated osteoclast formation in fetal mouse metatarsal explants or in adult mice and determined the effect on angiogenesis. Suppression of osteoclast formation with osteoprotegerin dose-dependently inhibited angiogenesis and osteoclastogenesis in metatarsal explants. Conversely, treatment with parathyroid hormone related protein (PTHrP) increased explant angiogenesis, which was completely blocked by osteoprotegerin. Further, treatment of mice with receptor activator of nuclear factor-κB ligand (RANKL) or PTHrP in vivo increased calvarial vessel density and osteoclast number. We next determined whether matrix metalloproteinase-9 (MMP-9), an angiogenic factor predominantly produced by osteoclasts in bone, was important for osteoclast-stimulated angiogenesis. The pro-angiogenic effects of PTHrP or RANKL were absent in metatarsal explants or calvaria in vivo, respectively, from Mmp9−/− mice, demonstrating the importance of MMP-9 for osteoclast-stimulated angiogenesis. Lack of MMP-9 decreased osteoclast numbers and abrogated angiogenesis in response to PTHrP or RANKL in explants and in vivo but did not decrease osteoclast differentiation in vitro. Thus, MMP-9 modulates osteoclast-stimulated angiogenesis primarily by affecting osteoclasts, most probably by previously reported migratory effects on osteoclasts. These results clearly demonstrate that osteoclasts stimulate angiogenesis in vivo through MMP-9.