Does incidence of rash predict treatment response to lapatanib in breast cancer?

Abstract

e11127 Background: Inflammatory papulopustular rash with acneiform distribution is a common dermatologic toxicity, which occurs in more than 30% of patients receiving lapatinib, a dual inhibitor of EGFR and HER2, for the treatment of HER2 over-expressing breast cancer. This adverse effect is a class effect of drugs that target EGFR, including erlotinib, cetuximab, and gefitinib and has been associated with superior treatment response. Although plausible, there is no evidence to date that the development of rash correlates with treatment response to lapatinib in breast cancer. We hypothesized that breast cancer patients who develop rash on lapatinib treatment will have a better treatment response. Methods: We prospectively enrolled 49 patients with locally advanced HER2-positive breast cancer (>/= 3 cm) on a clinical trial of neoadjuvant monotherapy with lapatinib (1500 mg per day for 6 weeks). Patients were followed for rash, which was graded using NCI CTCAE criteria, during the course of lapatinib treatment. Any rash that was considered lapatinib-related was counted as an event regardless of the severity. Primary endpoint of the trial was overall response rate, assessed by objective bidimensional tumor measurements and defined by at least 50% reduction in the product of the largest perpendicular diameters of the breast lesion according to standard WHO criteria. Results: Forty-seven patients were evaluated and were divided into two groups: with and without rash. We found that among 32 (68%) patients who experienced rash, 22 (69%) responded to treatment; whereas, 10 (31%) did not. Out of 15 (32%) patients who did not have rash, 11 (73%) responded to treatment; whereas, 4 (27%) did not. The difference was not statistically significant (p= 1.0, Fisher’s exact two-sided test). Two patients, who did not have post-treatment measurements, were excluded from analysis. Conclusions: In the neoadjuvant setting, incidence of rash did not predict clinical efficacy with lapatinib monotherapy in treatment-naïve locally advanced HER2-positive breast cancer patients.