Journal Article

First-Line Herceptin® Monotherapy in Metastatic Breast Cancer

Shak, Steven, Slamon, Dennis J., Murphy, Maureen, Tripathy, Debu, Novotny, William F., Gutheil, John C., Burchmore, Michael, Fehrenbacher, Louis, Vogel, Charles L., Harris, Lyndsay N., Stewart, Stanford J., Cobleigh, Melody A.

2001

Overview

The pivotal phase II and III Herceptin ® trials proved the efficacy and safety of second- or third-line single-agent Herceptin and first-line Herceptin in combination with chemotherapy, respectively. In the current trial, 114 patients were randomized to one of two dose groups of first-line Herceptin monotherapy: standard dose of 4 mg/ kg initial dose followed by 2 mg/kg intravenous (i.v.) weekly; or high dose of 8 mg/kg initial dose followed by 4 mg/kg i.v. weekly. The regimen was generally well tolerated. A similar incidence of adverse events was demonstrated in the two dose groups with the possible exception of acute infusion-related events such as fever and chills as well as rash and dyspnea, which appear to be more prevalent in the higher dose group. The overall response rate was 26% and response rates were similar between the two dose groups (24% for the standard Herceptin dose group and 28% for the high Herceptin dose group). Subgroup analysis determined a higher response rate in IHC 3+ patients (35%) and FISH-positive patients (41%). When women with stable disease for ≧6 months were included with responders, the clinical benefit rate in IHC 3+ patients was 47%. Median survival was 24.4 months, which is comparable with the survival rate seen in the pivotal phase III combination trial (25 months). Therefore, single-agent Herceptin is an important new option for the first-line treatment of HER2-positive metastatic breast cancer patients.

• Publisher: Karger,S. Karger AG
• Subject: Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized / Antineoplastic agents / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - adverse effects / Antineoplastic Agents - therapeutic use / Biological and medical sciences / Biomarkers, Tumor - analysis / Breast Neoplasms - chemistry / Breast Neoplasms - drug therapy / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Clinical Trials, Phase II as Topic / Clinical Trials, Phase III as Topic / Combined Modality Therapy / Disease Progression / Disease-Free Survival / Female / Fever - chemically induced / Gynecology. Andrology. Obstetrics / Heart Diseases - chemically induced / Humans / Immunotherapy / Mammary gland diseases / Medical sciences / Neoplasm Metastasis / Neoplasm Proteins - analysis / Pain - virology / Palliative Care / Pharmacology. Drug treatments / Randomized Controlled Trials as Topic / Receptor, ErbB-2 - analysis / Receptors, Estrogen - analysis / Safety / Salvage Therapy / Survival Analysis / Trastuzumab / Treatment Outcome / Tumors
• ISBN: 3805573278, 9783805573276