Abstract
PURPOSE: We investigated the pattern of rash, diarrhea, and hepatic adverse events (AEs) secondary to lapatinib and their association with age and pathologic complete response (pCR) in the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (NeoALLTO) phase III trial. PATIENTS AND METHODS: Patients with HER2-positive early breast cancer were randomly assigned to receive lapatinib (Arm A), trastuzumab (Arm B), or their combination (Arm C) for 6 weeks followed by the addition of paclitaxel for 12 weeks before surgery. We investigated the frequency and time to developing each AE according to age (≤ 50 v > 50 years) and their association with pCR in a logistic regression model adjusted for age, hormone receptors, tumor size, nodal status, planned breast surgery, completion of lapatinib administration, and treatment arm. RESULTS: Only patients randomly assigned to arms A and C were eligible (n = 306). Younger patients (≤ 50 years) experienced significantly more rash compared with older patients (74.4% v 47.9%; P < .0001). Diarrhea and hepatic AEs were observed in 78.8% and 41.2% of patients, respectively, with no differences in rate or severity or time of onset according to age. Early rash (ie, before starting paclitaxel) was independently associated with a higher chance of pCR, mainly in patients older than 50 years (odds ratio [OR] = 3.76; 95% CI, 1.69 to 8.34) but not in those ≤ 50 years (OR = 0.92; 95% CI, 0.45 to 1.88; P for interaction = .01). No significant association was observed between pCR and diarrhea or hepatic AEs. CONCLUSION: Our results indicate that the frequency and clinical relevance of lapatinib-related rash is largely dependent on patient age.