Pattern of rash, diarrhea, and hepatic toxicities secondary to lapatinib and their association with age and response to neoadjuvant therapy: Analysis from the NeoALTTO trial
Journal
Journal of Clinical Oncology
Journal Volume
31
Journal Issue
36
Pages
4504-4511
Date Issued
2013
Author(s)
Azim H.A.
Agbor-Tarh D.
Bradbury I.
Dinh P.
Baselga J.
Di Cosimo S.
Greger Jr. J.G.
Smith I.
Jackisch C.
Kim S.-B.
Aktas B.
Vuylsteke P.
Hsieh R.K.
Dreosti L.
Eidtmann H.
Piccart M.
De Azambuja E.
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. ? 2013 by American Society of Clinical Oncology.
SDGs
Other Subjects
alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; cyclophosphamide; epidermal growth factor receptor 2; epirubicin; fluorouracil; gamma glutamyltransferase; hormone receptor; lapatinib; paclitaxel; trastuzumab; antineoplastic agent; epidermal growth factor receptor 2; ERBB2 protein, human; lapatinib; monoclonal antibody; paclitaxel; quinazoline derivative; trastuzumab; tumor marker; antineoplastic agent; monoclonal antibody; quinazoline derivative; add on therapy; adjuvant therapy; adult; age; alanine aminotransferase blood level; alkaline phosphatase blood level; article; aspartate aminotransferase blood level; bilirubin blood level; breast cancer; breast surgery; cancer size; cancer surgery; controlled study; diarrhea; disease severity; drug dose reduction; drug eruption; drug withdrawal; early cancer; gamma glutamyl transferase blood level; human; liver toxicity; lymph node; multicenter study; multiple cycle treatment; pathologic complete response; phase 3 clinical trial (topic); preoperative period; priority journal; randomized controlled trial; treatment duration; treatment planning; treatment response; adjuvant chemotherapy; age; aged; breast tumor; chemically induced disorder; chemistry; controlled clinical trial; diarrhea; drug administration; drug eruption; female; incidence; methodology; middle aged; pathology; statistical model; time; toxic hepatitis; adjuvant therapy; Breast Neoplasms; chemically induced; diarrhea; Drug Eruptions; Drug-Induced Liver Injury; procedures; Adult; Age Factors; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Diarrhea; Drug Administration Schedule; Drug Eruptions; Drug-Induced Liver Injury; Female; Humans; Incidence; Logistic Models; Middle Aged; Neoadjuvant Therapy; Paclitaxel; Quinazolines; Receptor, erbB-2; Time Factors; Tumor Markers, Biological; Adult; Age Factors; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Diarrhea; Drug Administration Schedule; Drug Eruptions; Drug-Induced Liver Injury; Female; Humans; Incidence; Logistic Models; Middle Aged; Neoadjuvant Therapy; Paclitaxel; Quinazolines; Receptor, ErbB-2; Time Factors; Tumor Markers, Biological
Publisher
American Society of Clinical Oncology
Type
journal article