Background: Overexpression/Amplification of the HER2 occurs in 15-18% of breast cancers. Adjuvant trastuzumab is now integrated in the care of most HER2-positive early stage breast cancers. However, an important question persists regarding the concurrent vs. sequential use of trastuzumab as adjuvant treatment in early stage breast cancer. A meta-analysis of randomized controlled trials (RCT) was undertaken to compare concurrent vs. sequential trastuzumab. The outcomes of interest were risk of recurrence, death and grade III and IV cardiac toxicity. Method: Systematic review of English literature retrieved from EMBASE (1980 to April 26, 2010), MEDLINE (1996 to April 26, 2010) and Cochrane database for the relevant studies. In addition, conference proceedings of ASCO and SABCS from 2004 to 2009 were searched for relevant abstracts. A manual search of the reference lists of the selected articles was performed in order to further identify relevant studies. The search strategy was conducted according to our well-defined inclusion and exclusion criteria. Our search strategy revealed 1262 citations. Only RCTs were included. The review was performed by 2 reviewers independently. The data analysis was conducted by Review Manager Version 5, which could not compare the number of recurrences and deaths head to head for concurrent vs. sequential trastuzumab. A Fixed effect model was used. When I square showed heterogeneity of >50%, sensitivity analysis was performed. Results: Six eligible trials were identified. Three RCTs used trastuzumab concurrently and 2 RCTs used trastuzumab sequentially. One RCT (NCCTG N9831) had 3 arms, chemo only control arm, sequential trastuzumab arm and concurrent trastuzumab arm. Pooled and sensitivity analysis of 4 RCTS comparing concurrent trastuzumab with chemotherapy showed total HR of 0.73 (P<0.00001) for reduction of recurrence and 0.78 (P=0.0006) for reducing the mortality. The pooled analysis of 3 RCTs comparing sequential trastuzumab with chemotherapy revealed total HR of 0.82 for reduction of recurrence (P<0.0001) and 0.93 for mortality (p=0.27). The cardiac toxicity in concurrent trastuzumab was in favour of control with risk ratio of 4.66 (P<0.00001) and in sequential treatment was also in favour of control with risk ratio of 9.90 (P<0.0001).

Conclusion: Concurrent trastuzumab with chemotherapy shows a greater improvement in DFS (HR: 0.73 vs. 0.82). HR for OS also favours concurrent trastuzumab (0.78 vs. 0.93). Cardiac toxicity in both concurrent and sequential trastuzumab favours control arms.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-12-03.