(ChemotherapyAdvisor) – For women with HER2-positive early breast cancer who do not or cannot receive adjuvant trastuzumab, lapatinib might provide a marginal benefit with respect to disease-free survival, exploratory analyses of a randomized phase 3 study suggest in the January 2013 issue of The Lancet Oncology.

The analyses were restricted to women with HER2-positive disease confirmed by central fluorescence in situ hybridization and were conducted after analysis of the intention-to-treat population in the placebo-controlled multicenter study showed no significant difference in disease-free survival between the lapatinib and placebo arms, noted Paul E. Goss, MD, of Massachusetts General Hospital, Boston, MA, and colleagues.

Between August 2006 and May 2008, 3,147 women with HER2-positive disease who had previously received adjuvant chemotherapy—but not trastuzumab—were randomly assigned to receive lapatinib 1500mg/day (n=1,571) or matching placebo (n=1,576) for 12 months or until disease recurrence. Patients were stratified by time since diagnosis, negative or positive lymph node involvement at diagnosis, and tumor hormone-receptor status. Primary end point was disease-free survival in the intention-to-treat population.

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After a median follow-up of 47.4 months in the lapatinib group and 48.3 in the placebo group, 210 (13%) disease-free survival events had occurred in the lapatinib group vs 264 (17%) in the placebo group (hazard ratio [HR] 0.83; 95% CI 0.70−1.00; P=0.053).

Among the women, 2,490 (79%) were HER2-positive. Of 1,230 confirmed HER2-positive patients in the lapatinib group and 1,260 in the placebo group, 157 (13%) and 208 (17%), respectively, had a disease-free survival event (HR 0.82, 95% 0.67−1.00; P=0.04). Serious adverse events occurred in 99 (6%) of 1,573 patients taking lapatinib and 77 (5%) of 1,574 patients taking placebo.

“Trastuzumab plus chemotherapy remains the standard of care for women with early-stage HER2-positive breast cancer,” Dr. Goss reported. “This trial provides evidence of the effect of adjuvant lapatinib on women with HER2-positive early breast cancer, justifying ongoing assessment in other trials, which are testing combined or sequential strategies with other anti-HER2 treatments to draw more definitive conclusions.”

An accompanying commentary noted, “it remains to be seen whether the benefit of administration of lapatinib with trastuzumab applies with other anti-HER2 drugs (eg, pertuzumab, trastuzumab emtansine), and, most importantly, whether combination regimens improve survival in early breast cancer.”

The study was funded by GlaxoSmithKline.