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TCH effective as adjuvant therapy for HER-2–positive breast cancer
SAN ANTONIO — Adjuvant therapy with the HER-2 targeted treatment trastuzumab in combination with the chemotherapy drugs docetaxel and carboplatin produced excellent postsurgical results in patients with HER-2–positive breast cancer without the use of an anthracycline, according to study results presented at the San Antonio Breast Cancer Symposium.
The phase 3, open-label BETH study included 3,509 patients divided into two cohorts.
The first cohort included 3,231 patients who were randomly assigned to six cycles of TCH [trastuzumab (Herceptin, Genentech) plus docetaxel and carboplatin] or TCH plus bevacizumab.
The second cohort included 278 patients treated with three cycles of anthracycline therapy with epirubicin in conjunction with trastuzumab, with or without bevacizumab (Avastin, Genentech).
Prior studies have shown anthracyclines dramatically improved outcomes in patients with HER-2–positive disease — extending DFS and OS by 3% to 5% — but were associated with long-term side effects, including leukemia and heart failure.
Dennis J. Slamon
In the BETH study, median follow-up was 38 months. At that time, DFS was 92% in both arms of the TCH cohort vs. 89% in the anthracycline cohort. Although the difference was not statistically significant, the anthracycline arm was “certainly not superior” to the non-anthracycline arm, according to Dennis J. Slamon, MD, PhD, director of clinical/translational research at the UCLA Jonsson Comprehensive Cancer Center, and professor of medicine and chief of the division of hematology/oncology at the UCLA Department of Medicine.
“Our new results, which surpassed our expectations, show that it really is not necessary to include an anthracycline as part of the treatment regimen to obtain really ideal results for patients with HER-2–positive breast cancer,” Slamon said. “The importance of the results lies in the fact that the TCH combination has a much better safety profile than anthracycline and trastuzumab combinations and is now equally effective.”
The addition of bevacizumab to adjuvant therapy was associated with increased adverse events, results showed. Incidence of hypertension (329 vs. 78; P<.0001); bleeding (42 vs. 9; P<.0001); congestive heart failure (23 vs. 12; P=.0621); proteinuria (21 vs. 1; P<.0001); and gastrointestinal perforations (11 vs. 1; P=.0031) was higher among patients who received bevacizumab.
“The addition of bevacizumab didn’t add any efficacy, but it certainly added some safety concerns,” Slamon said during a press conference.
Because it will be difficult to develop treatment regimens with better response rates, future research should focus primarily on improving the safety of adjuvant regimens, Slamon said.
“With [trastuzumab], we’re at 92% DFS, so the room for further improvement is getting smaller and smaller,” Slamon said. “The good news is, we’ve really changed the natural history of HER-2–positive breast cancer with these new targeted therapeutics.”
For more information:
Slamon DJ. Abstract #S1-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2013; San Antonio.
Disclosure: The study was supported by Roche/Genentech. Slamon has served as an advisor to Roche and Genentech.