In individual participant data and trial-level meta-analyses reported in JAMA Network Open, Gulia et al found that disease-free survival with adjuvant trastuzumab given for less than 1 year was noninferior to 1 year of trastuzumab therapy in patients with early breast cancer. In addition, the shorter treatment duration was associated with a reduced risk of congestive heart failure.
Study Details
The study included data from six randomized clinical trials comparing 1 year of adjuvant trastuzumab with less than 1 year of treatment in patients with early breast cancer reported between January 2005 and June 2019. Five of the trials had extractable individual participant data for meta-analysis.
The primary outcome measure was disease-free survival. All six trials had noninferiority designs. A disease-free survival P value < .025 was considered significant for concluding noninferiority of shorter duration compared with 1 year of trastuzumab. If the upper limit of the 95% confidence interval (CI) of the estimated hazard ratio (HR) of shorter duration vs 1 year of trastuzumab in individual participant data and trial-level analyses was less than 1.3 (the median noninferiority margin of the randomized clinical trials), then shorter duration treatment was considered noninferior.
“The results of this meta-analysis suggest that shorter duration of trastuzumab is noninferior to its 1-year administration with respect to disease-free survival with fewer cardiac toxic effects.”— Gulia et al
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Key Findings
The individual participant data analysis included 11,376 patients. Disease-free survival at 5 years was 85.42% in the shorter-duration group vs 87.12% in the 1-year group, with an estimated hazard ratio of 1.14 (95% CI = 1.03–1.25; P for noninferiority = .004). Overall survival at 5 years was 92.39% vs 93.46% (HR = 1.17, 95% CI = 1.02–1.33).
The trial-level analysis included 11,603 patients. For shorter duration vs 1 year of trastuzumab, the hazard ratio for disease-free survival was 1.15 (95% CI = 1.04–1.26; P for noninferiority = .002). The hazard ratio for overall survival was 1.17 (95% CI = 1.03–1.33).
The risk of congestive heart failure was lower in patients with a shorter duration of treatment (3.9% vs 6.9%, relative risk [RR] = 0.53, 95% CI = 0.38–0.74; P < .001), as was the risk of developing asymptomatic left-ventricular ejection fraction decline (5% vs 7%, RR = 0.71, 95% CI = 0.50–1.00; P = .049).
The investigators concluded, “The results of this meta-analysis suggest that shorter duration of trastuzumab is noninferior to its 1-year administration with respect to disease-free survival with fewer cardiac toxic effects. The absolute survival differences between the two 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.”
Sudeep Gupta, MD, DM, of the Department of Medical Oncology, Tata Memorial Centre, Mumbai, is the corresponding author for the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
