A single-arm phase II trial of first-line paclitaxel in combination with lapatinib in HER2-overexpressing metastatic breast cancer.

INTRODUCTION

Lapatinib, an orally active tyrosine kinase inhibitor of epidermal growth factor receptor ErbB1 (EGFR) and ErbB2 (HER2), has activity as monotherapy and in combination with chemotherapy in HER2-overexpressing metastatic breast cancer (MBC).

METHODS

This phase II single-arm trial assessed the safety and efficacy of first-line lapatinib in combination with paclitaxel in previously untreated patients with HER2-overexpressing MBC. The primary endpoint was the overall response rate (ORR). Secondary endpoints were the duration of response (DoR), time to response, time to progression, progression-free survival (PFS), overall survival, and the incidence and severity of adverse events. All endpoints were investigator- and independent review committee (IRC)-assessed.

RESULTS

The IRC-assessed ORR was 51% (29/57 patients with complete or partial response) while the investigator-assessed ORR was 77% (44/57). As per the IRC, the median DoR was 39.7 weeks, and the median PFS was 47.9 weeks. The most common toxicities were diarrhea (56%), neutropenia (44%), rash (40%), fatigue (25%), and peripheral sensory neuropathy (25%).

CONCLUSIONS

First-line lapatinib plus paclitaxel for HER2-overexpressing MBC produced an encouraging ORR with manageable toxicities. This combination may be useful in first-line treatment for patients with HER2-overexpressing MBC and supports the ongoing evaluation of this combination as first-line therapy in HER2-overexpressing MBC.

Copyright © 2010 S. Karger AG, Basel.