Meta-Analysis Supports Shorter Adjuvant Trastuzumab Duration In Nonmetastatic Breast Cancer

Author: By Shreeya Nanda, Senior medwireNews Reporter 

medwireNews: Adjuvant trastuzumab durations of less than a year are a valid option for patients with early-stage breast cancer, say the authors of a meta-analysis demonstrating noninferiority of the shorter regimens to its 1-year administration with regard to disease-free survival (DFS). 

In addition, the rates of cardiac adverse events were lower with the shorter schedules versus 1-year use, say Sudeep Gupta and colleagues from Tata Memorial Centre in Mumbai, India. 

And they write in JAMA Network Open: “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 team notes, however, that additional analysis suggested “more favorable” hazard ratios (HRs) for DFS and overall survival (OS) for the three trials that used 6 months of trastuzumab in the experimental group compared with those using 9–12 weeks, “indicating that abbreviating trastuzumab duration to 6 months may be a more appropriate strategy.” 

The researchers extracted individual patient data for 11,376 participants of five randomised controlled trials that compared a shorter duration with 1 year of adjuvant trastuzumab, and found that the 5-year DFS rates were 85.42% and 87.12%, respectively. This gave an HR of 1.14, where the upper limit of the 95% confidence interval was within the noninferiority threshold of 1.30 (the median of the thresholds across the included trials). 

The 5-year OS rates were 92.39% and 93.46% for the shorter duration and 1-year trastuzumab groups, respectively, and the HR was 1.17. 

Sudeep Gupta and team note that the results of the trial-level analysis, which included an additional study, “closely matched” those from the individual-level analysis, with respective HRs for DFS and OS of 1.15 and 1.17. 

Further analysis showed that the HRs for DFS and OS versus 1-year trastuzumab were a respective 1.27 and 1.25 for the trials investigating 9–12 weeks of trastuzumab, while the corresponding HRs were 1.10 and 1.14 for trials evaluating a 6-month schedule. 

However, the investigators did not identify any subgroups that derived a statistically significant DFS benefit with a shorter trastuzumab duration, “perhaps because of inadequate power for some interactions.” 

The incidence of congestive heart failure was significantly lower among patients who received shorter durations of trastuzumab than those who received the 1-year course, at 3.9% versus 6.9% (relative risk [RR]=0.53), and there was also a trend towards a reduced risk of asymptomatic decline in left ventricular ejection fraction (5.0 vs 7.0%; RR=0.71). 

The study authors point out, however, that “longer duration of trastuzumab was associated with lower all-cause mortality compared with shorter durations”, which “is likely a reflection of the reversibility of trastuzumab-associated cardiac toxic effects.” 

Reference  

Gulia S, Kannan S, Badwe R, Gupta S. Evaluation of 1-year vs shorter durations of adjuvant trastuzumab among patients with early breast cancer. An individual participant data and trial-level meta-analysis. JAMA Netw Open; 3:e2011777. Published online 24 August 2020. doi: 10.1001/jamanetworkopen.2020.11777