Abstract P3-12-03: Risk of infectious complications in breast cancer patients treated with trastuzumab: A meta-analysis
Authors: Funakoshi Tomohiro , Suzuki Maya , Muss Hyman B 
Published: May 2015

Abstract
Background
Serious infections related to the anti-HER2 monoclonal antibody trastuzumab has been reported in clinical trials. It is not yet clear whether trastuzumab increases infection risk or not. We performed a systematic review and meta-analysis to assess the risk of infections associated with trastuzumab.
Patients and methods
We searched PubMed and the ASCO online database of meeting abstracts up to January 2014 for relevant clinical trials. Eligible studies included randomized controlled trials (RCTs) of trastuzumab for breast cancer patients that reported adequate safety data for grade 3-4 infection, febrile neutropenia, neutropenia, or leukopenia. Grade3 and 4 infection is defined as "IV antimicrobial agents, interventional radiology or operative intervention indicated" and "life-threatening consequences (e.g., septic shock)", respectively. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated. RRs and summary incidence were calculated using random-or fixed-effects models depending on the heterogeneity of included studies. Prespecified exploratory subgroup analyses were performed according to treatment setting (neoadjuvant or adjuvant vs. metastatic setting) and therapy used with trastuzumab (combination vs. best supportive care (BSC) or single agent therapy) with regard to the RRs.
Results
A total of 10,094 patients from 13 trials of trastuzumab were included. The use of trastuzumab was associated with an increased risk of high-grade infection (RR, 1.21; 95% CI, 1.07-1.37; P=0.002) and febrile neutropenia (RR, 1.28; 95% CI, 1.08-1.52; P=0.004). The incidence of grade 3-4 infection and febrile neutropenia related to trastuzumab and control was 8.5% (95% CI 4.5-15.4%) vs. 6.9% (95% CI 4.0–11.6%) and 12.0% (95% CI, 8.1-17.4%) vs. 9.9% (95% CI, 6.6-14.6%), respectively. There was no significant increase in a risk of high-grade neutropenia (RR, 1.07; 95% CI, 0.98-1.68; P=0.15) or leukopenia (RR, 1.07; 95% CI, 0.94-1.23; P=0.31) in patients receiving trastuzumab. The results of exploratory subgroup analyses were shown in table1.
RR of high-grade infection and febrile neutropenia according to treatment setting and therapy used with trastuzumab.High-grade infectionFebrile neutropeniaNo. of trialsRR (95%CI)PNo. of trialsRR (95%CI)PTreatment settingNeoadjuvant/Adjuvant setting71.21 (1.06-1.38)0.00461.27 (1.06-1.52)0.008Metastatic setting61.21 (0.82-1.79)0.3431.38 (0.79-2.42)0.26Therapy used with trastuzumabCombination therapy71.18 (1.04-1.35)0.0161.27 (1.06-1.52)0.008BSC/Single agent therapy71.47 (1.02-2.12)0.0431.38 (0.79-2.42)0.26BSC, best supportive care; RR, relative risk
Conclusions
Treatment with trastuzumab is associated with a 1.21-fold increased risk of high-grade infection and a 1.28-fold increased risk of febrile neutropenia compared with control. In order to obtain the maximum therapeutic benefit from trastuzumab, clinicians should be aware of the increased infection risk and perform careful monitoring especially when it is used with combination chemotherapy in the neoadjuvant and adjuvant setting.
Citation Format: Tomohiro Funakoshi, Maya Suzuki, Hyman B Muss. Risk of infectious complications in breast cancer patients treated with trastuzumab: A meta-analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-03.