SABCS 2008: Neoadjuvant Trastuzumab Should Be a Standard for Locally Advanced Breast Cancer

Zosia Chustecka

December 12, 2008

December 12, 2008 (San Antonio, Texas) — Neoadjuvant use of trastuzumab (Herceptin, Roche) with chemotherapy for locally advanced HER2-positive breast cancer should become a new standard of treatment, say researchers presenting new data from a large phase 3 clinical trial here at the 31st Annual San Antonio Breast Cancer Symposium.

This would represent a new use for trastuzumab; so far it is approved for use only in the adjuvant setting. Physicians are already using trastuzumab before surgery, even though this is an off-label use, because there were dramatic results showing a benefit in the neoadjuvant setting from a previous smaller trial carried out at the MD Anderson Cancer Center, in Houston, Texas (J Clin Oncol. 2005;23:3676-3685).

This latest study is a phase 3 trial in 228 patients, partly funded by the manufacturer, and the results will likely be used in the submission for regulatory approval for a new indication. The final results of the trial, known as NOAH (Neo-Adjuvant Herceptin), were presented at the meeting by Luca Gianni, MD, from the Istituto Nazionale Tumori Milano, in Milan, Italy.

An Unmet Medical Need

Locally advanced breast cancer, which includes inflammatory breast cancer, is an area of unmet medical need, Dr. Gianni commented. It is a particularly aggressive form of the disease, with a prognosis of 3 to 6 years, compared with more than 10 years for other forms of breast cancer.

In the NOAH study, adding trastuzumab to chemotherapy containing an anthracycline and a taxane administered before surgery significantly improved event-free survival, Dr. Gianni reported. At a median follow-up of 3 years, event-free survival with the combination was 70%, compared with 53% for chemotherapy alone, so the relative risk for recurrence was almost halved (hazard ratio, 0.56; P = .006).

In addition, trastuzumab plus chemotherapy produced a complete pathologic response in nearly twice as many patients as chemotherapy alone (39% vs 20%; P = .002). The overall response rate was also significantly increased, to 89% with the combination vs 77% with chemotherapy alone (P = .02). There was a trend toward increased overall survival for the combination group, but this was not significant, and longer follow-up is needed, Dr. Gianni said.

All subgroups of patients benefited from the addition of trastuzumab, Dr. Gianni noted. The combination was superior to chemotherapy alone in patients with inflammatory breast cancer and in those with noninflammatory breast cancer, in those who were hormone-receptor positive and those who were hormone-receptor negative, and in those who had or did not have a complete pathologic response.

The combination of trastuzumab with chemotherapy in the neoadjuvant setting was well tolerated, with acceptable cardiac safety, Dr. Gianni commented.

"These data establish preoperative trastuzumab with chemotherapy as a standard treatment option in women with locally advanced HER2-positive breast cancer," Dr. Gianni concluded.

It is a very reasonable alternative.

"It is a very reasonable alternative, I would say, for these patients," said Carlos Arteaga, MD, from Vanderbilt University, in Nashville, Tennessee, who moderated a press conference during the meeting. Physicians are already using trastuzumab in the neoadjuvant setting, he said. There are some patients who are treated with chemotherapy alone before surgery, and then have trastuzumab added on after surgery, but these are a minority. The previous study from the MD Anderson Cancer Center showed a 65% complete pathologic response rate with neoadjuvant trastuzumab and chemotherapy, which "is not too far from these latest results," he said. That result was so dramatic that the study was stopped early, he told Medscape Oncology.

31st Annual San Antonio Breast Cancer Symposium (SABCS): Abstract 31. Presented December 12, 2008.

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