Preclinical data from ErbB2-positive cell lines have identified a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade of ErbB2 is more effective than monotherapy. This randomised open-label phase III study compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC).

The researchers equally randomised 296 women with ErbB2-positive MBC, who experienced progression on prior trastuzumab-containing regimens, to lapatanib monotherapy or lapatinib in combination with trastuzumab. The primary end point was progression-free survival (PFS). #

The following results were reported:

• In the intent-to-treat population (N = 296) who received a median of three prior trastuzumab-containing regimens, the median PFS was 8.1 weeks with lapatinib monotherapy compared with 12.0 weeks with the combination treatment  (hazard ratio [HR] = 0.73; 95% CI, 0.57 to 0.93; P = 0.008).

• The percentage of patients whose disease was progression free at 6 months (secondary endpoint) doubled in the combination arm compared with the monotherapy arm (28% v 13%, respectively; P= 0 .003).

• No statistical difference in overall survival (secondary endpoint) (HR = 0.75; 95% CI, 0.53 to 1.07; P = 0.106).

• There was no significant difference in overall response rate (secondary endpoint) between the two arms (10.3% with the combination therapy v 6.9% with lapatinib monotherapy; P =0.46).

• The clinical benefit rate reached statistical significance between the treatment groups with 24.7% of patients in the combination arm experiencing clinical benefit compared with 12.4% in the monotherapy arm (P =0.01).

• The most frequent adverse events in both arms were diarrhoea, rash, nausea, and fatigue; diarrhoea was higher in the combination arm (P =0.03).

• The incidence of symptomatic and asymptomatic cardiac events was low (combination therapy = 2% and 3.4%; monotherapy = 0.7% and 1.4%, respectively).

The authors concluded that “despite disease progression on prior trastuzumab-based therapy, lapatinib in combination with trastuzumab significantly improved PFS and CBR versus lapatinib alone, thus offering a chemotherapy-free option with an acceptable safety profile to patients with ErbB2-positive MBC”.