Adjuvant therapy with trastuzumab plus paclitaxel yielded a 3-year recurrence rate of < 2% in an uncontrolled, nonrandomized study involving women who had small stage I HER2-positive breast cancers, according to a report published online Jan. 8 in the New England Journal of Medicine.
Currently no standard treatment is recommended for such patients, and clinicians must weigh the generally favorable outcomes for small, stage I tumors that aren’t targeted with adjuvant chemotherapy against the potential for considerable toxic effects from adjuvant chemotherapy. Clinical trials of trastuzumab have focused on patients with more advanced cancers. “Although patients with stage I HER2-positive tumors are expected to derive a smaller absolute benefit from adjuvant therapy than those with larger or node-positive tumors, they remain at more than minimal risk for a recurrence of breast cancer,” said Dr. Sara M. Tolaney of the department of medical oncology, Dana-Farber Cancer Institute, Boston, and her associates.
Their industry-sponsored single-group study involved 406 patients with a median age of 55 years (range, 24-85 years) whose breast adenocarcinomas measured no more than 3 cm. After undergoing surgical excisions, all the study participants were assigned to receive weekly IV paclitaxel and IV trastuzumab for 12 weeks, after which trastuzumab could be continued at the same weekly dose for 40 weeks or the regimen could be changed to a slightly higher dose every 3 weeks for 40 weeks.
A total of 356 patients (87.7%) completed the full year of adjuvant trastuzumab. Women who opted for partial- or whole-breast irradiation commenced that treatment after completing paclitaxel and while taking trastuzumab, and those who chose hormonal therapy also began taking those agents after completing paclitaxel and while taking trastuzumab. Median follow-up was 4 years (maximum, 6.2 years).
At 3-year follow-up, the rate of cancer-free survival was 98.7%, which was higher than would have been predicted by historical data; there were four distant and four local or regional metastases. According to the study’s statistical design, adjuvant trastuzumab would be considered successful if the 3-year recurrence rate were 5% or lower and there were 39 or fewer metastases, Dr. Tolaney and her associates said (N. Engl. J. Med. 2015 Jan. 8 [doi:10.1056/NEJM0a1406281]).
A total of 6% of patients withdrew from the study because of treatment-related adverse effects. The most important known adverse effect of trastuzumab is left ventricular dysfunction, so cardiac function was assessed at several intervals during the year of active therapy. Two patients (0.5%) developed grade 3 LV dysfunction during treatment, and both recovered after the drug was discontinued. Thirteen patients (3.2%) showed an asymptomatic decline in ejection fraction that led to an interruption in trastuzumab therapy; this normalized in 11 of them, who then resumed the treatment. Seven patients developed grade 3 or 4 allergic reactions, and only one of them was able to resume the treatment.