Trastuzumab Benefits Women with Locally Advanced or Inflammatory Breast Cancer

Adapted from the NCI Cancer Bulletin.

Findings from an international clinical trial suggest a new treatment option for some women with aggressive types of breast cancer. In the NOAH trial, women treated with trastuzumab (Herceptin®) and chemotherapy before surgery (neoadjuvant) and trastuzumab again after surgery (adjuvant) had a reduced risk of the disease recurring or progressing after 3 years compared with women who received pre-surgical chemotherapy but no trastuzumab before or after surgery. The findings were published January 30, 2010, in The Lancet.

The 230 women enrolled in the trial had either locally advanced or inflammatory breast cancer that was HER2-positive. Although trastuzumab has been shown to improve overall survival (OS) in women with HER2-positive early stage and metastatic breast cancer, the drug has not been closely studied in women with these intermediate stages of breast cancer, the research team wrote.

Patients who were randomly assigned to receive trastuzumab took the drug for a total of 1 year. Three-year event-free survival (EFS) —with an event defined as disease recurrence, progression, or death from any cause—was 71 percent in patients treated with trastuzumab and 56 percent in those who did not receive it. The pathological complete response rate, or no detectable presence of cancer, was nearly doubled among the women who received trastuzumab.

To date, there is no statistically significant improvement in OS among the women who received trastuzumab. This could be due to the fact that 17 percent of the women in the chemotherapy-alone arm also received adjuvant trastuzumab, while some other patients received the drug following a recurrence, explained the trial’s principal investigator, Luca Gianni, M.D., of the Italian National Cancer Institute, in a Lancet podcast.

There were no significant issues with cardiac side effects, which have been a recurring problem in other breast cancer trials involving trastuzumab and doxorubicin (Adriamycin®), a drug that was part of the chemotherapy regimen used in the trial.

According to Massimo Cristofanilli, M.D., chair of the Department of Medical Oncology at Fox Chase Cancer Center, pathological complete response "is the most important prognostic factor" in women with the breast cancer types included in this trial. The low rates of cardiac side effects, he noted, were likely due to the facts that patients in the trial had not been pretreated, had optimal heart function, and had received cumulative doses of doxorubicin that were below those typically associated with cardiotoxicity.

Editor’s Note: Updated results published March 19, 2014, in The Lancet Oncology have shown that the statistically significant improvement in EFS with trastuzumab was sustained after longer follow up. OS was also better in women who received trastuzumab, although the difference was still not statistically significant. Five-year EFS and OS were 58 percent and 74 percent, respectively, in the trastuzumab-treated patients, compared with 43 percent and 63 percent, respectively, in the patients treated with chemotherapy only. No additional serious adverse events were reported.

Subgroup analyses showed that, among the 68 women who had a pathological complete response (45 of the 117 women treated with trastuzumab and 23 of the 118 women treated with chemotherapy alone), those treated with trastuzumab were statistically significantly more likely to be alive without having had their disease progress or recur at 5 years than those treated with chemotherapy alone. The researchers also found that pathological complete response was associated with EFS outcomes only in women who received trastuzumab. This subgroup analysis by treatment response suggests that the “addition of trastuzumab resulted not only in more patients achieving a pathological complete response, but also in a different quality of response,” wrote the researchers.