Abstract P3-15-05: Risk and consequences of neutropenic complications with adjuvant use of trastuzumab and chemotherapy in women with metastatic breast cancer
Authors: Weycker D , Li X , Kartashov A , Barron R , Edelsberg J , Xu H , Girardi V , Lyman G 
Published: August 2014

Background: Between 20-30% of women with metastatic breast cancer (MBC) have tumors that overexpress human epidermal growth factor receptor-2, and many receive adjuvant trastuzumab and chemotherapy. In clinical trials, adjuvant use of trastuzumab increased the incidence of severe/febrile neutropenia–a potentially fatal side effect–among women receiving traditional chemotherapy. Risks and consequences of chemotherapy-induced neutropenic complications (CINC) among this patient population in US clinical practice are not well documented.

Methods: A retrospective cohort design and US healthcare claims data (2007-2011) were utilized. The first observed chemotherapy course with trastuzumab, and each cycle and episode of CINC within the course, were identified; use of prophylaxis with colony-stimulating factors (CSF) and oral antimicrobial (AMB) agents in each cycle also was identified. CINC was ascertained using broad (diagnosis of neutropenia, fever, and/or infection) and narrow (diagnosis of neutropenia) definitions, and was stratified by care setting; for CINC requiring outpatient care only, receipt of intravenous AMB also was required. A validation study found that the risk of FN may lie between CINC risk when the latter is defined using broad and narrow criteria (Weycker, BMC Health Services Research 2013).

Results: Among 1679 subjects, most common regimens were trastuzumab in combination with paclitaxel (32%), carboplatin+docetaxel (24%), and vinorelbine (22%). Across regimens, use of CSF prophylaxis in cycle 1 ranged from 1.7-49.6%; an additional 10.2-19.8% first received CSF prophylaxis after cycle 1. Risk of CINC (broad definition) during the course ranged from 7.0-14.6%; of subjects with CINC, 86-93% had CINC in the inpatient setting and 25-47% experienced CINC in cycle 1. For CINC requiring inpatient care (broad definition, n = 175 episodes across all regimens), hospital mortality was 5.0% (95%CI: 2.4-8.8), hospital LOS was 7.4 (6.5-8.3) days, and healthcare expenditures were $15,024 ($11,810-$18,238); for CINC requiring outpatient care only (broad definition, n = 40 episodes across all regimens), healthcare expenditures were $1,757 ($836-$2,678).

 PAC + T-MAB (n = 530)TCH (n = 395)VIN + T-MAB (n = 362)DOC + T-MAB (n = 205)PAC + CAR + T-MAB (n = 187)Age, mean (SD)56.5 (11.1)53.1 (11.0)56.3 (11.2)56.1 (10.7)52.9 (9.7)No. Cycles per Course, mean (SD)10.1 (11.7)4.8 (2.8)8.7 (10.1)7.1 (7.3)7.5 (5.9)Dosing Schedule*,%     QW61.95.866.929.860.4Q2W13.25.816.68.38.0Q3W12.571.17.745.423.5Q4W+12.517.28.816.68.0Prophylaxis in Cycle 1,%     CSF2.849.61.720.512.3AMB (oral)5.76.48.34.913.4CINC Risk,% (95%CI)     Broad Definition     Course10.1 (7.9-13.0)13.9 (10.8-17.6)7.7 (5.4-10.9)14.6 (10.4-20.1)7.0 (4.1-11.5)Cycle 14.2 (2.8-6.2)6.6 (4.5-9.5)1.9 (0.9-3.9)4.4 (2.3-8.1)2.7 (1.1-6.1)Narrow Definition     Course4.2 (2.8-6.2)8.4 (6.0-11.5)4.1 (2.5-6.7)5.4 (3.0-9.4)3.7 (1.8-7.5)Cycle 12.1 (1.2-3.7)3.5 (2.1-5.9)0.8 (0.3-2.4)2.4 (1.0-5.6)0.5 (0.1-3.9)*Observed duration of cycle 1

Conclusion: Among women receiving adjuvant trastuzumab and chemotherapy for MBC in US clinical practice, use of CSF/AMB prophylaxis varies widely across regimens as does the risk of CINC.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-05.