Shorter Trastuzumab Treatment Duration Not Inferior in Breast Cancer Patients

A study comparing outcomes for breast cancer patients who received one year of adjuvant trastuzumab treatment versus a shorter length of time did not find interior outcomes for the latter group.

“The standard adjuvant treatment ERBB2 (formerly HER2 or HER2/neu)-positive breast cancer includes chemotherapy and 1 year of trastuzumab, a recombinant, humanized monoclonal antibody that targets the ERBB2 receptor,” the study authors explained. “Although trastuzumab is a well-tolerated drug, it is associated with cardiac dysfunction.8 An overview analysis found increased risk of congestive heart failure (CHF) (relative risk [RR], 5.1) with trastuzumab-based regimens (2.5%) compared with nontrastuzumab regimens (0.4%), and a meta-analysis showed that the absolute risk of high-grade CHF with 1 year of adjuvant trastuzumab was 1.4% vs no detectable risk with a 9-week course of trastuzumab (RR, 3.2).”

To investigate the drug further, the researchers queried PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings for relevant randomized, clinical trials  from Jan. 1, 2005, to June 30, 2019. They collected individual patient disease-free survival (DFS) and overall survival (OS) curves data from the studies, and the curves for each trial and the complete patient population were reconstructed; these data, along with published estimates, were used to calculate DFS and OS hazard ratios (HRs). DFS was the main outcome; secondary outcomes were OS and cardiac toxic effects.

The median DFS noninferiority margin (range) of six trials was 1.3 (1.15–1.53). Five of the trials provided individual patient data encompassing 11,376 patients; there were 1,659 DFS events and 871 deaths. The five-year DFS for shorter duration trastuzumab was 85.42% (95% confidence interval [CI], 84.41% to 86.38%), compared to 87.12% (95% CI, 86.15% to 88.02%) for the one-year group (HR=1.14; 95% CI, 1.03 to 1.25; 1-sided P for noninferiority=0.004). OS in the shorter duration trastuzumab group was 92.39% (95% CI, 91.61% to 93.10%), compared to 93.46% (95% CI, 92.73%-94.13%) for the one-year group (HR=1.17; 95% CI, 1.02 to 1.33).

Trial-level published estimates from all six trials encompassed 11,603 patients, 1,760 DFS events, and 930 deaths. The HRs for DFS and OS were 1.15 (95% CI, 1.04-1.26; 1-sided P for noninferiority=0.002) and 1.17 (95% CI, 1.03 to 1.33), respectively. The shorter duration trastuzumab group had a significantly reduced risk for congestive heart failure (relative risk, 0.53; 95% CI, 0.38 to 0.74).

The study was published in JAMA Network Open.

“The results of this meta-analysis suggest that shorter duration of trastuzumab is noninferior to its 1-year administration with respect to DFS with fewer cardiac toxic effects. The absolute survival differences between the 2 groups are small, and shorter durations could be therapeutically appropriate in situations of toxic effects or resource constraints, especially among patients with clinically low-risk disease,” the authors concluded.