Adjuvant trastuzumab for HER2-positive early BC: 9 weeks or 1 year?

For patients with HER2-positive early breast cancer (BC), 1 year of adjuvant trastuzumab remains standard of care (SoC) as noninferiority is not demonstrated for a shortened 9-week course of treatment in the final analysis of the phase III ShortHER trial. However, long-term data from the trial provide reassurance in case early discontinuation is needed in low-risk patients.

In the noninferiority trial, 1,254 patients with HER2-positive early BC (median age, 55 years; postmenopausal, 64 percent; stage I, 41 percent; stage II, 44 percent; 0 positive lymph node, 54 percent; hormone receptor–positive, 68 percent) were randomized 1:1 to receive adjuvant treatment with anthracycline-taxane combination chemotherapy plus 1 year or 9 weeks of trastuzumab. Coprimary endpoints were disease-free survival (DFS) and overall survival (OS), with a hazard ratio (HR) of <1.29 set as noninferiority margin. [J Clin Oncol 2023;doi:10.1200/JCO.23.00790]

Final analysis of the trial, after a median follow-up of 9 years, showed a 10-year DFS rate of 77 percent vs 78 percent in the 1-year vs 9-week trastuzumab arm (HR, 1.06; 90 percent confidence interval [CI], 0.86–1.31), while 10-year OS rate was 89 percent vs 88 percent (HR, 1.15; 90 percent CI, 0.85–1.56).

By nodal status, 10-year DFS rate in the 1-year vs 9-week arm was 81 percent vs 85 percent (HR, 0.75; 95 percent CI, 0.51–1.10) in patients with N0 disease, 77 percent vs 79 percent (HR, 1.11; 95 percent CI, 0.70–1.76) in those with N1–3 disease, and 63 percent vs 53 percent (HR, 1.84; 95 percent CI, 1.14–2.97) in those with N4+ disease, respectively.

OS rate at 10 years was 89 percent vs 95 percent (HR, 0.57; 95 percent CI, 0.30–1.10) in patients with N0 disease, 92 percent vs 89 percent (HR, 1.37; 95 percent CI, 0.69–2.73) in those with N1–3 disease, and 84 percent vs 64 percent (HR, 1.87; 95 percent CI, 1.01–3.46) in those with N4+ disease, respectively.

“The updated analysis shows that 1-year trastuzumab is the SoC for patients with HER2-positive early BC, as noninferiority cannot be claimed for the 9-week treatment,” the researchers concluded. “However, numerically, the differences for patients at low or intermediate risk [N0/N1–3] is negligible, while patients with N4+ disease have a clear benefit with 1-year trastuzumab.”

“These long-term data can reassure clinicians in case of early discontinuation of adjuvant trastuzumab for any reason in patients at low risk,” they suggested. “Importantly, these updated results might also have a role in facilitating access to a less expensive treatment to the thousands of patients worldwide who cannot afford the cost of 1 year of trastuzumab.”

In Western countries, for example, up to 15 percent of patients in pivotal trials had to stop trastuzumab before 1 year for a variety of reasons, while a proportion of patients are unable to start trastuzumab treatment for financial reasons. [JAMA Netw Open 2023;6:e2255388]

“In low- and middle-income countries, trastuzumab is available for only 15 percent of the patients, while access to the drug would imply catastrophic expenses for 68 percent of the patients,” the researchers noted. [Lancet Oncol 2021;22:1367-1377]