Trastuzumab emtansine safe and effective in HK patients with metastatic HER2-positive breast cancer
Trastuzumab emtansine (T-DM1) is safe and effective for use in Chinese patients with HER2-positive advanced breast cancer, according to data from five oncology centres in Hong Kong.
The retrospective study also showed a median duration of response of 17.3 months, with 8.1 percent of patients experiencing a complete response and 21.6 percent experiencing a partial response.
Patients with recurrent or metastatic disease had received either one line of trastuzumab with chemotherapy (24.3 percent), two lines of therapy (29.7 percent), or three or more lines of therapy (45.9 percent) prior to T-DM1 therapy.
More than one-third of the patients had received at least two lines of palliative chemotherapy (70.3 percent) composed of either taxanes, capecitabine or vinorelbine.
Around half of the patients had received one or more lines of palliative endocrine therapy such as tamoxifen (21.6 percent), aromatase inhibitors (40.5 percent) or ovarian ablation (18.9 percent).
At the beginning of the study, more than half of the patients had three or more disease sites involved, such as the lymph nodes (73 percent), lungs (54.1 percent) and bones (51.4 percent).
“Similar to two previous international studies [TH3RESA and EGF104900] among heavily pretreated populations, the use of anti-HER2 therapy yielded meaningful clinical benefits,” the authors commented. [Lancet Oncol 2014;15:689-699; J Clin Oncol 2010;28:1124-1130]
The median progression-free survival (PFS) in the current study was 6 months (6-month PFS rate, 51.6 percent; 12-month PFS rate, 23.1 percent). The median overall survival (OS) was not reached (6-month OS rate, 82.1 percent; 12-month OS rate, 74.4 percent).
Around one-third of the patients had either stable disease (29.7 percent) or progressive disease (32.4 percent) after T-DM1 therapy.
Most patients in the study (89 percent) were started on the standard T-DM1 dose of 3.6 mg/kg once every 3 weeks for a median number of 6 cycles (range, 1–43).
“Although the results [of the study] could not be compared with reported prospective trials, patients were representative and treatment outcomes reflect routine clinical practice,” the authors said.
Grade 3/4 toxicities occurred in some patients and included thrombocytopenia (13.5 percent), elevated alanine transaminase levels (8.1 percent), anaemia (5.4 percent) and hypokalaemia (2.7 percent).
Other toxicities that occurred in more than 10 percent of patients included elevated alkaline phosphatase levels, hyponatraemia, neutropenia, leukopenia, fatigue, elevated serum creatinine levels, and diarrhoea.
“This study demonstrated that T-DM1 therapy provided a meaningful PFS with a favourable toxicity profile among heavily pretreated patients with HER2-positive advanced breast cancer. Further research is needed to identify biomarkers that predict sensitivity and resistance to anti-HER2 agents. This will predict patients’ response to therapy and help optimize clinical benefits,” they concluded.
T-DM1 is an antibody-drug conjugate that incorporates the HER2-targeted antitumour properties of trastuzumab with the cytotoxic activity of the microtubule inhibitor DM1. [Cancer Res 2008;68:9280-9290; Mol Cancer Ther 2010;9:2689-2699]