Mumbai, India—
Is it safe and effective for patients with early breast cancer to have a shorter duration of adjuvant trastuzumab use?

That was the question prompting a study published in JAMA Network Open.  Trastuzumab is monoclonal antibody targeting human epidermal growth factor receptor 2 and has been shown to improve survival rates but has some cardiovascular risks. 

Indian researchers from the Tata Memorial Centre at Homi Bhabha National Institute conducted a meta-analysis of individual patient data from five randomized clinical trials, including 11,376 participants, and trial-level data from six randomized clinical trials with 11,603 participants. Results indicate that shorter duration of adjuvant trastuzumab was noninferior to 1 year of treatment, when considering disease-free survival, and was associated with lower rates of cardiac toxic effects. 

“The findings of this study suggest that a shorter duration of adjuvant trastuzumab may be the preferred option for patients with low-risk disease or a predisposition to cardiac toxic effects,” the authors write, noting, “The optimum duration of adjuvant trastuzumab among patients with early breast cancer is uncertain but of great therapeutic relevance.”

For the meta-analysis, researchers searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2005, to June 30, 2019, for relevant randomized clinical trials (RCTs). Eligible trials were those that were randomized, compared a shorter duration with 1 year of trastuzumab as adjuvant treatment, and included patients with early breast cancer.

The primary outcome was defined as disease-free survival (DFS), with overall survival and cardiac toxic effects as secondary outcomes. Trastuzumab is considered to be a well-tolerated drug, but it is associated with cardiac dysfunction, specifically with congestive heart failure, the study points out.

The authors ultimately focused on six eligible RCTs with a median DFS noninferiority margin of 1.3 (range, 1.15-1.53), five of which had extractable individual patient data for 11, 376 patients, 1,659 DFS events, and 871 deaths.

The study determined that, for shorter duration versus 1 year of trastuzumab, the 5-year DFS was 85.42% (95% CI, 84.41%-86.38%) versus 87.12% (95% CI, 86.15%-88.02%) (hazard ratio [HR], 1.14; 95% CI, 1.03-1.25, 1-sided P for noninferiority = .004), and overall survival was 92.39% (95% CI, 91.61%-93.10%) versus 93.46% (95% CI, 92.73%-94.13%) (HR, 1.17; 95% CI, 1.02-1.33).

When researchers used trial-level published estimates from six RCTs, including 11,603 patients, 1,760 DFS events, and 930 deaths, the HR for DFS was 1.15 (95% CI, 1.04-1.26; 1-sided P for noninferiority = .002) and 1.17 (95% CI, 1.03-1.33) for OS. The authors emphasize that they found significantly less risk of congestive heart failure with shorter duration trastuzumab (relative risk, 0.53; 95% CI, 0.38-0.74).

“In this study, a shorter duration of adjuvant trastuzumab was noninferior to its 1-year administration and resulted in lower rates of cardiac toxic effects,” the authors conclude. “These results suggest that a shorter duration may be the preferred option for patients with low-risk disease or a predisposition to cardiac toxic effects.”

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