Negative Findings Show Herceptin Fails to Benefit Breast Cancer Subgroup

A trial to determine the value of Herceptin (trastuzumab) plus standard adjuvant chemotherapy in patients with low levels of HER2 protein has shown no significant efficacy, confusing investigators who launched the trial based on opposing results from two earlier studies.

The findings were presented today at the San Antonio Breast Cancer Symposium (SABCS).

In a slide presented by Louis Fehrenbacher, M.D., medical director of Kaiser Permanente Oncology Clinical Trials and an oncologist with the Kaiser Permanente Vallejo Medical Center, at the SABCS press conference, the invasive disease-free survival (IDFS) lines for both arms of the study — with and without Herceptin — were plotted on top of each other and a difference was virtually indistinguishable. Fehrenbacher said that the primary objective of improving IDFS was not met, neither were any of the secondary endpoints, and “no trends of efficacy were seen.”

“We could magnify this slide, you still couldn’t see a difference between those two arms whatsoever,” he said. “There was no hint of efficacy in any of the stratification variables.”

The five-year IDFS rate was 89.6 percent among the 1,640 patients who received Herceptin and 89.2 percent among the 1,630 patients who did not. Investigators said the findings were no different whether patients were subdivided by HER2 immunohistochemistry (IHC) level, extent of lymph node involvement or hormone receptor status.

Fehrenbacher noted that the event rate was essentially equal between the two groups — 134 for the chemotherapy arm and 130 for chemotherapy plus Herceptin. There were no statistically significant differences in the five-year estimates for recurrence-free interval, distant recurrent-free interval, and overall survival between those who received Herceptin and those who did not.

Although the National Surgical Adjuvant Breast and Bowel Project (NSABP) study of Herceptin and chemotherapy demonstrated improved outcomes for patients with early stage HER2-low breast cancer, the study (NSABP B-47) is valuable because it makes clear that patients with this form of the disease “can unequivocally know that Herceptin is not a beneficial treatment for them,” Fehrenbacher said.

Herceptin can cause serious adverse effects such as cardiotoxicity, so these findings help ensure that patients are not treated unnecessarily, Investigators added.

A moderator for the press conference noted that although SABCS normally does not present negative findings from trials, an exception was made in this case because of the importance to the large number of patients whose test outcomes are HER2-low and for whom studies like this offer hope for potential treatment.

“It doesn’t answer the question completely, but certainly if there’s a high suspicion or increased suspicion, one can certainly test other areas of the tumor,” Fehrenbacher said.

Asked if changes in testing procedures over time may have contributed to the findings, Fehrenbacher said that, if anything, testing has gotten better, and in the case of B-47, the testing was tightened up to ensure higher quality results.

He said the results came as a surprise, particularly because of the sharpness of the demarcation between those who benefit from Herceptin and those who do not.