SAN ANTONIO — The antibody-drug conjugate trastuzumab emtansine (T-DM1) does not improve survival outcomes compared with the standard of care in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.
Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the "first-line treatment for HER2-positive advanced breast cancer, regardless of age," said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium (SABCS) 2023.
However, he noted that the standard-of-care regimen appears to be "intolerable mentally and physically" in those older than 65 years, and "impairs" quality of life.
Therefore a "new standard treatment with less toxicity and noninferior efficacy for older patients is needed," said Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.
Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.
Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.
Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.
At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).
There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).
However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.
Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.
The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).
Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.
Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a "detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment," said Shimomura.
Virginia Kaklamani, MD, co-director of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, told Medscape Medical News that the trial shows T-DM1 could be "a good alternative to our first line therapy in HER2+ metastatic breast cancer" for some patients.
"It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials," she said.
The study was funded by the Japanese National Cancer Center.
Shimomura declares relationships with Daiichi-Sankyo; Pfizer, Inc; AstraZeneca K.K.; Chugai Pharmaceutical Co. Ltd; Eli Lilly Japan K.K.; MSD Co. Ltd; Eisai Co. Ltd; Gilead Sciences; Taiho Pharmaceutical Co. Ltd.
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