ADJUVANT KADCYLA FOR BREAST CANCER

The treatment of HER2-positive, early stage breast cancer has taken "one more step toward personalized medicine and reduced mortality" thanks to the results of the KATHERINE trial, according to Daniel Hayes, MD, a medical oncologist at the University of Michigan Rogel Cancer Center in Ann Arbor.

He says the trial is a "game changer" for patients who have residual disease after initial drug treatment and surgery, in an editorial published online February 13 in the New England Journal of Medicine.

The editorial accompanies publication of the trial results, which were first presented at the San Antonio Breast Cancer Symposium in December 2018, as reported by Medscape Medical News.

The trial enrolled patients with stage I to III HER2-positive disease who were found to have residual disease upon excision after standard neoadjuvant treatment (chemotherapy plus a HER2-targeted drug).

The trialists randomized these patients to post-surgery ado-trastuzumab emtansine(T-DM1; Kadcyla, Roche) or the current adjuvant standard — trastuzumab — for 14 cycles.

T-DM1 is an antibody–drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1) approved for use in patients with HER2-positive metastatic breast cancer.

The intent of the trial was to see whether T-DM1 could improve outcomes in this residual disease population. These early stage patients who have lingering disease after pre-surgery drug treatment have a higher risk of disease recurrence or death than those who have a pathological complete response (ie, no residual disease), previous studies have shown.

The intent was met, suggested Hayes. The results amount to a "remarkable benefit" and are "impressive and clinically meaningful," he says.

Specifically, among 1486 randomly assigned patients (743 in the T-DM1 arm and 743 in the trastuzumab arm), invasive disease or death, which was the primary endpoint, had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%).

The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group — an absolute difference of 11.3%.

"T-DM1 offers a major opportunity to improve long-term outcomes," Hayes summarizes.

There is a price, however, for the improved efficacy, he adds. "Caveat emptor: doctors and patients need to be aware that the side effects of this regimen are more common than with trastuzumab alone, and occasional severe toxic effects need to be considered," Hayes writes.

Hayes stresses that the neoadjuvant standard of care remains chemotherapy plus HER2-targeted therapy for patients with newly diagnosed HER2-positive breast cancer.