Adjuvant Trastuzumab-Paclitaxel May Reduce Stage I/II HER2-Positive Disease Recurrence

Women with small HER2-positive breast cancers may benefit from adjuvant paclitaxel plus trastuzumab

medwireNews: Trial findings indicate that adjuvant paclitaxel plus trastuzumab may minimise the likelihood of early invasive recurrence in women with small, human epidermal growth factor receptor 2 (HER2)-positive breast tumours.

The 3-year rate of invasive disease-free survival was 98.7% among the 406 women with stage I or II cancers smaller than 3 cm in dimension, and who were node-negative or had more than one node positive for micrometastase, report Eric Winer, from Dana–Farber Cancer Institute in Boston, Massachusetts, USA, and co-workers.

This rate was based on four cases of local or regional recurrence and two cases of distant recurrence, but excluded women who developed contralateral breast cancer or other types of tumour, and non-breast cancer-related deaths.

Writing in The New England Journal of Medicine, the researchers say their findings “are better than expected” in the context of historical findings that indicate a 5-year risk of recurrence of between 5% and 30% for women who did not receive trastuzumab or, in some cases, any chemotherapy.

However, they note that their patient population included a higher proportion of hormone receptor-positive tumours than those of earlier studies, and that given these tumour types’ association with late recurrence, all patients should be followed-up for 10 years.

The uncontrolled, single-centre trial consisted of paclitaxel 80 mg/m2 per week plus intravenous trastuzumab 4 mg/kg on day 1 followed by weekly 2 mg/kg treatment for 12 weeks. Patients were then given a weekly or 3-weekly dose of trastuzumab for 40 weeks.

The team believes that a prospective randomised trial of the regimen would not have been feasible because of mounting retrospective evidence supporting use of trastuzumab in patients with low-risk tumours.

“Instead, we opted for a regimen of trastuzumab plus chemotherapy that would be associated with fewer toxic effects than the established regimens for patients with a higher risk of recurrence”, the researchers explain.

In all, 3.2% of patients experienced at least one grade 3 episode of neuropathy during the initial 12 weeks of treatment. And 8.6% of patients had a grade 2 or more severe allergic reaction, with only one patient able to continue with treatment.

A clinically significant but asymptomatic decline in ejection fraction leading to trastuzumab interruption was reported for 3.2% of patients, all but two of whom were able to continue with treatment after normalisation. Two (0.5%) patients developed reversible grade 3 systolic dysfunction of the left ventricle during the extended trastuzumab phase.

Thus, the researchers caution that their study “does not provide data to support the use of trastuzumab-based chemotherapy in all patients with small HER2-positive tumors, and there will be many patients with T1a disease and some with T1b disease who will decide with their physicians to avoid the toxic effects of a trastuzumab-based regimen.”


Tolaney SM, Barry WT, Dang CT, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 2015; 372: 134–141. DOI:10.1056/NEJMoa1406281

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