An analysis of the phase III adjuvant ALTTO trial showed that early rash was associated with better clinical outcome with lapatinib (Tykerb) treatment of HER2-positive breast cancer, as reported by Sonnenblick et al. It had been previously found that early rash was associated with improved pathologic complete response rate in patients with breast cancer receiving neoadjuvant lapatinib.
In ALTTO, women with HER2-positive early breast cancer were randomly assigned to receive trastuzumab (Herceptin), lapatinib, their sequence, or their combination for 1 year. Early lapatinib-related rash was defined as that occurring within 6 weeks of starting treatment. Among 6,098 lapatinib-treated patients, 3,973(65.2%) were included in a landmark analysis at 8 weeks; of them, 1,389 (35.0%) had developed early rash.
After median follow-up of 4.5 years, on multivariate analysis, the development of early rash was associated with a trend toward improved disease-free survival (hazard ratio [HR] = 0.87, P = .10) and significantly improved overall survival (HR = 0.63, P < .001) compared with absence of early rash. Compared with 2,051 patients in the trastuzumab group, patients in the trastuzumab/lapatinib combination group who developed early rash (n = 692) had significantly improved disease-free survival (HR = 0.72, P = .01) and overall survival (HR = 0.59, P = .01), whereas those in the combination group without rash (n = 1,319) had nonsignificant improvement in disease-free survival (HR = 0.93, P = .46) and overall survival (HR = 0.92, P = .55). Time-dependent analysis suggested that development of rash at some point during treatment was predictive of lapatinib benefit both in combination and sequential regimens with trastuzumab.
The investigators concluded:
Our results indicate that early development of rash identifies patients who derive superior benefit from lapatinib-based therapy.