Background: Maintaining high relative dose intensity (RDI) has been associated with improved disease-free survival, progression-free survival, and overall survival of patients with breast cancer treated in the adjuvant setting. Neutropenia and related complications, such as febrile neutropenia, are common side effects of myelosuppressive chemotherapy that can lead to dose delays, dose reductions, and reduced RDI. Primary prophylaxis with colony-stimulating factors (CSFs) can reduce the duration and severity of neutropenia and the incidence of febrile neutropenia, thereby supporting high RDI. For patients with stage IV breast cancer, dose delays and dose reductions are frequently used to manage toxicity associated with myelosuppressive chemotherapy. However, the prevalence and impact of reduced RDI in the metastatic disease setting is poorly understood.

Objective: To estimate mean chemotherapy RDI and incidences of dose delays, dose reductions, RDI <85%, and primary CSF prophylaxis among women with stage IV breast cancer receiving first-line chemotherapy.

Methods: Using the McKesson Specialty Health/US Oncology iKnowMed™ electronic health record (HER) database, we retrospectively identified adult women with stage IV breast cancer who initiated first-line, intravenous, myelosuppressive chemotherapy from January 2007 to December 2010 in community oncology practices in the US. Patients were assigned to chemotherapy cohorts based on myelosuppressive agents received in cycle 1 and planned regimen information in the database. Standard chemotherapy regimens were defined based on NCCN breast cancer guidelines and clinical studies. Mean RDI and incidences of dose delays ≥7 days, dose reductions ≥15%, and RDI <85% in any cycle during the course of chemotherapy were evaluated relative to the standard chemotherapy regimen. Primary CSF prophylaxis was defined as first receipt of CSF during the first 5 days of chemotherapy cycle 1. Patients were followed for up to 6 months after chemotherapy initiation.

Results: This study included 1471 patients with stage IV breast cancer who received myelotoxic chemotherapy. The most common chemotherapy regimens in the metastatic setting were taxane-based, and endpoints for the three most common chemotherapy regimens (n = 307) are shown in the Table.

  Paclitaxel/ Bevacizumaba Albumin-bound Paclitaxelb Paclitaxelc 
176 75 56 
Age, mean (SD) years 58.2 (11.9) 63.6 (12.4) 61.8 (13.8) 
RDI, mean (SE) 89.0% (1.9) 89.1% (3.1) 89.0% (3.2) 
RDI <85% 37.5% 41.3% 26.8% 
Dose delays ≥7 days 36.9% 22.7% 32.1% 
Dose reductions ≥15% 40.9% 61.3% 8.9% 
CSF primary prophylaxis 0% 1.3% 3.6% 
  Paclitaxel/ Bevacizumaba Albumin-bound Paclitaxelb Paclitaxelc 
176 75 56 
Age, mean (SD) years 58.2 (11.9) 63.6 (12.4) 61.8 (13.8) 
RDI, mean (SE) 89.0% (1.9) 89.1% (3.1) 89.0% (3.2) 
RDI <85% 37.5% 41.3% 26.8% 
Dose delays ≥7 days 36.9% 22.7% 32.1% 
Dose reductions ≥15% 40.9% 61.3% 8.9% 
CSF primary prophylaxis 0% 1.3% 3.6% 

aPaclitaxel 80-90 mg/m2 on days 1, 8, and 15 and bevacizumab 10 mg/kg on days 1 and 15 (cycle length 28 days). Paclitaxel dose at cycle 1, day 1 was defined as the standard dose for this regimen; bAlbumin-bound paclitaxel 100 mg/m2 on days 1, 8, and 15 (cycle length 28 days); cPaclitaxel 80 mg/m2 (cycle length 7 days).

Conclusions: Chemotherapy dose delays, dose reductions, and reduced RDI were common in patients with stage IV breast cancer. The impact of RDI on progression-free and overall survival is being evaluated and will be presented.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-09.