Rabbit Anti-Human ErbB3 (phospho Tyr1222) monoclonal antibody, clone L.06.2

Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000mg in Cohort 1; 500mg in Cohorts 2 and 3) plus pertuzumab (840mg loading dose [LD] followed by 420mg in Cohorts 1 and 2; 420mg without LD in Cohort 3) every 3weeks, plus paclitaxel (80mg/m(2) weekly in all cohorts). Patients in Cohort 3 received prophylactic loperamide treatment. Results Diarrhea grade 3 was a dose-limiting toxicity of Cohort 1 defining the maximum tolerated dose of lumretuzumab when given in combination with pertuzumab and paclitaxel at 500mg every three weeks. Grade 3 diarrhea decreased from 50% (Cohort 2) to 30.8% (Cohort 3) with prophylactic loperamide administration and omission of the pertuzumab LD, nonetheless, all patients still experienced diarrhea. In first-line MBC patients, the objective response rate in Cohorts 2 and 3 was 55% and 38.5%, respectively. No relationship between HER2 and HER3 expression or somatic mutations and clinical response was observed. Conclusions Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated with a high incidence of diarrhea. Despite the efforts to alter dosing, the therapeutic window remained too narrow to warrant further clinical development. Trial registration: on ClinicalTrials.gov with the identifier NCT01918254 first registered on 3rd July 2013.

Basal cell carcinomas (BCCs) are the most common malignant skin tumors, with variable prognosis and recurrence rates, depending on histopathological subtypes. The study analyzed the immunoexpression of epidermal growth factor receptors (EGFRs) in 53 cases of nodular, adenoid and morpheaform BCCs in relation to clinico-pathological associated parameters. We found significant differences in the expression of EGFR, HER2 and HER3 reported to histological BCC types. The nodular type presented the weakest expression of EGFRs, while the morpheaform type had a high expression of all receptors and the adenoid type an increased expression only in case of EGFR and HER2. This study supports the involvement of EGFR, HER2 and HER3 in BCC aggressiveness of and in tumor differentiating towards different histological subtypes.