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ESMO 2018: Short-HER Trial Examines Abbreviated Course of Trastuzumab in Some HER2-Positive Early Breast Cancers

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Key Points

  • Patients with low- and intermediate-risk had similar 5-year disease-free survival with a 9-week course of trastuzumab (88%) as with 1 year.
  • Their risk of cardiac events was nearly three times lower.

Women with HER2-positive early breast cancer with small tumors have similar disease-free survival and lower risk of cardiac toxicity with a 9-week course of adjuvant trastuzumab (Herceptin) compared to those treated for 1 year, according to a subgroup analysis of the Short-HER trial reported by Conte et al at the European Society for Medical Oncology (ESMO) 2018 Congress (Abstract 191PD_PR).

Current ESMO guidelines recommend 1 year of anti-HER2 antibody therapy as part of standard adjuvant treatment for patients with HER2-positive early breast cancer based on the duration of treatment used in pivotal registration trials. There is interest in whether a shorter course of trastuzumab could potentially achieve similar efficacy with lower risk of side effects and costs.

The Short-HER trial randomly assigned 1,254 patients with HER2-positive early breast cancer to either 9 weeks or 1 year of treatment with trastuzumab, with both groups also receiving chemotherapy. Results after a median follow-up of 6 years published in the Journal of Clinical Oncology showed the short course did not achieve noninferiority but was associated with a reduction in the rate of severe cardiac toxicity.

New Analysis

In the newest analysis, researchers looked at whether there are subgroups of patients where a shorter course of trastuzumab may be noninferior to a longer course. Multivariate analysis showed that pathologic tumor size (pT) and nodal status (N) were independent prognostic factors for disease-free survival.

They identified three prognostic groups:

  • Low-risk (pathologic tumor size [pT] < 2 cm and N0), accounting for 37.5% of patients
  • Intermediate-risk (pT < 2 cm and any N category), accounting for 51.9%
  • High-risk (pT > 2 cm and N4+), accounting for 10.5% of the patient population.

Results showed that patients with low- and intermediate-risk had similar 5-year disease-free survival with a 9-week course of trastuzumab (88%) as with 1 year (89%; hazard ratio [HR] = 1.02, 95% confidence interval [CI] = 0.78–1.33), but their risk of cardiac events was nearly three times lower (4.5% vs 12.8%, relative risk = 2.88, 95% CI = 1.85–4.47). Women at low and intermediate risk of relapse accounted for 89% of patients in the study.

“The study was underpowered because of difficulties in recruiting patients in a reasonable time, so noninferiority could not be claimed based on the results,” said lead author Pierfranco Conte, MD, Professor of Oncology at the University of Padua and Director of the Division of Medical Oncology at the Instituto Oncologico Veneto, Padua, Italy. He added, “Based on our data, 1 year [of] trastuzumab remains the standard treatment for women with HER2-positive early breast cancer.”

However, Dr. Conte added, “Physicians can stop trastuzumab before 1 year in patients who develop a cardiac event during treatment without compromising efficacy and can consider shorter-duration trastuzumab treatment in patients at risk of cardiac toxicity and a low or intermediate risk of breast cancer relapse.” He suggested that consideration of shorter-duration trastuzumab may also facilitate access to patients who cannot afford a longer course.

Commenting on the study for ESMO, Nadia Harbeck, MD, PhD, Head of the Breast Center, University of Munich, said in a statement, “The results of this analysis showed that patients with a high tumor load definitely derive substantial benefit from longer-duration trastuzumab.”

She added, “The results may impact clinical decision-making, although it is an exploratory analysis of a negative trial so does not meet the criteria to be practice-changing. I think it will influence clinicians and patients in that if patients cannot complete 1 year of trastuzumab, those patients with low tumor burden can feel reassured that they have not lost out on efficacy.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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