Delay in initiation of adjuvant trastuzumab therapy leads to decreased overall survival and relapse-free survival in patients with HER2-positive non-metastatic breast cancer

Abstract

Trastuzumab reduces the risk of relapse in women with HER2-positive non-metastatic breast cancer, but little information exists on the timing of trastuzumab initiation. The study investigated the impact of delaying the initiation of adjuvant trastuzumab therapy for >6 months after the breast cancer diagnosis on time to relapse, overall survival (OS), and relapse-free survival (RFS) among patients with non-metastatic breast cancer. Adult women with non-metastatic breast cancer who initiated trastuzumab adjuvant therapy without receiving any neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012. Two study cohorts were defined based on the time from breast cancer diagnosis to trastuzumab initiation: >6 months and ≤6 months. The impact of delaying trastuzumab initiation on time to relapse, OS, and RFS was estimated using Cox regression models adjusted for potential confounders. Of 2749 women in the study sample, 79.9 % initiated adjuvant trastuzumab within ≤6 months of diagnosis and 20.1 % initiated adjuvant trastuzumab >6 months after diagnosis. After adjusting for confounders, patients who initiated trastuzumab >6 months after the breast cancer diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab within ≤6 months of diagnosis (hazard ratios [95 % CIs]: 1.51 [1.22-1.87], 1.54 [1.12-2.12], and 1.43 [1.16-1.75]; respectively). The results of this population-based study suggest that delays of >6 months in the initiation of trastuzumab among HER2-positive non-metastatic breast cancer patients are associated with a higher risk of relapse and shorter OS and RFS.

Keywords: HER2-positive non-metastatic breast cancer; Overall survival; Relapse-free survival; Trastuzumab.

Fig. 1

Sample selection flowchart. ^aInternational statistical classification of diseases, 9th revision, clinical modification [ICD-9-CM] code 174.x; ^bFrom January 1, 2003 to December 31, 2012; ^cTwo consecutive diagnoses of secondary neoplasms (ICD-9-CM 196.x-199.x, excluding codes that may be used to indicate locally advanced breast cancer: 196.0, 196.1, 196.3, and 198.2), within 60 days of each other; ^dChemotherapy, targeted or hormonal therapy

Fig. 2

Study design. ^aTrastuzumab was first approved in 1998 for the treatment of breast cancer in the metastatic setting, and then approved in 2006 in the adjuvant setting; the study included 494 patients without evidence of metastatic disease who received trastuzumab between 2003 and 2006. ^bAdjuvant regimen type was identified based on the chemotherapy and/or targeted therapies received in the period between the breast cancer surgery and 28 days after the initiation of trastuzumab. OS overall survival, RFS relapse-free survival

Fig. 3

Comparison of unadjusted RFS between study cohorts. RFS relapse-free survival