Findings from the phase III KATHERINE trial show that patients with residual HER2+ breast cancer after neoadjuvant treatment are half as likely to develop invasive disease recurrence if they are treated with T-DM1 instead of trastuzumab, the current standard of care.

Historically, patients with early-stage HER2-positive breast cancer and residual invasive disease—after neoadjuvant chemotherapy alongside HER2-targeted agents, chiefly trastuzumab (Herceptin; Genentech)—have faced a higher likelihood of invasive recurrence following surgery than patients with no remaining invasive disease. Investigators have been searching for a more effective treatment option for these patients than additional trastuzumab therapy, the current standard of care.

According to recent findings from the phase III KATHERINE trial, patients in this high-risk population who receive the antibody–drug conjugate ado-trastuzumab emtansine (T-DM1/Kadcyla; Genentech) instead of additional trastuzumab are half as likely to develop recurrence.

“Both the magnitude and the consistent degree of benefit across all subgroups of patients in the study were remarkable and pleasantly surprising,” said Charles Geyer Jr., MD, of Virginia Commonwealth University Massey Cancer Center in Richmond, lead author of the study, which was presented during the 2018 San Antonio Breast Cancer Symposium in Texas in December, and concurrently published (N Engl J Med 2018 Dec 5 [Epub ahead of print]).

graphic

Given its greater effectiveness at preventing recurrence of some breast cancers after neoadjuvant therapy, T-DM1 will likely replace standard trastuzumab treatment for certain women, according to Charles Geyer Jr., MD.

KATHERINE enrolled a total of 1,486 patients who had received neoadjuvant treatment that included a taxane with trastuzumab and were found to have residual disease at the time of surgery. They were randomly assigned to receive 14 cycles of either T-DM1 or trastuzumab. T-DM1 reduced the risk of recurrence or death by 50%; at 3 years, 88.3% of patients in this group were free of invasive disease, compared with 77% in the trastuzumab arm. The superiority of T-DM1 was consistent regardless of patient characteristics, including menopausal and hormone receptor status, the amount of residual disease at surgery, and lymph node involvement.

Side effects were more frequent with T-DM1, chiefly peripheral sensory neuropathy, reduced platelet counts, and elevation of liver enzymes. However, most adverse events in both arms of the trial were mild, said Geyer, and most toxicities in the T-DM1 arm were resolved with dose reductions.

“From the available data, it appears that the benefits of T-DM1 will far outweigh its toxicity” in this patient population, said Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center in Seattle, WA, who was not involved in the trial.

Both Geyer and Davidson believe that these findings are likely to change the way oncologists practice—even though the FDA hasn't yet approved T-DM1 for this indication. “Since T-DM1 is already an FDA-approved agent for advanced breast cancer and oncologists are versed in its use, I expect they will now recommend T-DM1 to women with residual HER2-positive disease in the post-neoadjuvant setting,” said Davidson.

Meanwhile, KATHERINE is scheduled to continue into the spring of 2023, said Geyer, which will provide a more complete picture of T-DM1's effects on survival over time. As well, ongoing trials are now investigating T-DM1's potential use as a neoadjuvant treatment. –Kristin Harper

For more news on cancer research, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.

©2019 American Association for Cancer Research.
2019
American Association for Cancer Research.