Improved OS in HER2+ breast cancer with trastuzumab emtansine vs capecitabine + lapatinib
Trastuzumab emtansine improved overall survival (OS) compared with capecitabine plus lapatinib in patients previously treated for locally advanced or metastatic, unresectable, HER2-positive breast cancer, according to final results of the phase III EMILIA* trial.
“[These] EMILIA study data reaffirm that trastuzumab emtansine is an efficacious and tolerable treatment for patients with previously treated HER2-positive metastatic breast cancer,” said the researchers, who highlighted that the OS benefit was evident despite more than one-fourth of patients on capecitabine plus lapatinib crossing over to trastuzumab emtansine.
Participants in this international (213 centres in 26 countries), open-label study were 991 patients (mean age 53 years) with HER2-positive, unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab and a taxane. They were randomized to receive intravenous trastuzumab emtansine (3.6 mg/kg every 3 weeks, n=495) or control (oral capecitabine [1,000 mg/m2 twice daily on days 1–14 of each 21-day cycle] plus lapatinib [1,250 mg once daily on days 1–21, n=496]) and were followed up for a median 47.8 and 41.9 months, respectively.
Median OS was longer in patients on trastuzumab emtansine vs control (29.9 vs 25.9 months, hazard ratio [HR], 0.75, 95 percent confidence interval [CI], 0.64–0.88). [Lancet Oncol 2017;doi:10.1016/S1470-2045(17)30312-1]
Twenty-seven percent (n=136) of patients in the control group crossed over to the trastuzumab emtansine group after a second OS analysis (median 51.2 weeks between cessation of control and initiation of trastuzumab emtansine) and were followed-up for a median 24.1 months.
Among patients censored at time of crossover, median OS was still longer in the group receiving trastuzumab emtansine vs control (29.9 vs 24.6 months, HR, 0.69, 95 percent CI, 0.59–0.82).
Fifty-one and 49 percent of patients who originally received trastuzumab emtansine received capecitabine and lapatinib (either alone or in combination), respectively, following trastuzumab emtansine discontinuation.
The incidence of grade 3 or worse adverse events was lower among patients on trastuzumab emtansine vs control (48 percent vs 60 percent). The most frequent grade 3 or higher adverse events among patients on trastuzumab emtansine were thrombocytopenia (14 percent), aspartate aminotransferase elevation (5 percent), and anaemia (4 percent), while diarrhoea (21 percent), palmar-plantar erythrodysaesthesia syndrome (18 percent), and vomiting (5 percent) were the most frequent grade 3 or higher adverse events among patients in the control group.
Two and one percent of patients in the trastuzumab emtansine and control groups, respectively, were affected by grade 3 or higher haemorrhage, while the incidence of grade 3 or higher cardiac dysfunction was low and comparable in both groups (<1 percent).
Of the nine deaths due to adverse events, five were deemed treatment-related, three and two in the trastuzumab emtansine and control groups, respectively.
“The final [OS] analysis of EMILIA lends further support to the early positioning of trastuzumab emtansine in the therapeutic sequence in patients with HER2-positive metastatic breast cancer,” said Dr Filippo Montemurro from the Candiolo Cancer Institute, Torino, Italy, in an editorial. [Lancet Oncol 2017;doi:10.1016/S1470-2045(17)30303-0]