Originally published as JCO Early Release 10.1200/JCO.2007.14.0590 on May 5 2008

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Efficacy and Safety of Lapatinib As First-Line Therapy for ErbB2-Amplified Locally Advanced or Metastatic Breast Cancer

Henry L. Gomez, Dinesh C. Doval, Miguel A. Chavez, Peter C.-S. Ang, Zeba Aziz, Shona Nag, Christina Ng, Sandra X. Franco, Louis W.C. Chow, Michael C. Arbushites, Michelle A. Casey, Mark S. Berger, Steven H. Stein, George W. Sledge

From the Instituto Nacional de Enfermedades Neoplásicas; Oncology, Hospital Alberto Sabogal, Lima, Peru; Rajiv Gandhi Cancer Institute and Research Centre, New Delhi; Jehangir Hospital and Medical Centre, Pune, India; National Cancer Centre, Singapore; Allama Iqbal Medical College, Lahore, Pakistan; University Malaya Medical Centre, Kuala Lumpur, Malaysia; University of Hong Kong and Queen Mary Hospital, Pokfulam, Hong Kong; Memorial Cancer Institute, Hollywood, FL; Medicine Development Center Oncology, GlaxoSmithKline, Collegeville, PA; and Indiana University School of Medicine, Indianapolis, IN

Corresponding author: Henry L. Gomez, MD, Instituto Nacional de Enfermedades, Neoplásicas, Avenida Angamos, Este 2520, Lima 34, Peru; e-mail: hgomez{at}inen.sld.pe

Purpose This study (EGF20009) assessed the efficacy and tolerability of two lapatinib administration schedules as first-line monotherapy in women with ErbB2-amplified locally advanced or metastatic breast cancer.

Patients and Methods Patients with ErbB2-amplified, locally advanced or metastatic breast cancer previously untreated in the metastatic setting were randomly assigned to one of two lapatinib dose cohorts and received either 1,500 mg once daily or 500 mg twice daily. Clinical response was assessed at weeks 8 and 12 and every 12 weeks thereafter.

Results A total of 138 patients were treated with lapatinib for a median of 17.6 weeks. The overall response rate (complete response [CR] plus partial response [PR]) was 24% in the intent-to-treat population, and 31% of patients derived clinical benefit (CR, PR, or stable disease for 24 weeks). The median time to response was 7.9 weeks, and the progression-free survival rates at 4 and 6 months were 63% and 43%, respectively. The most common lapatinib-related adverse events (AEs) were diarrhea, rash, pruritus, and nausea, and these events were primarily grade 1 or 2. There were no significant differences in clinical activity or the AE profile between the dosing schedules.

Conclusion Lapatinib demonstrated clinical activity and was well tolerated as first-line therapy in ErbB2-amplified locally advanced or metastatic breast cancer. This study supports further evaluation of lapatinib in first-line and early-stage ErbB2-overexpressing breast cancer.

published online ahead of print at www.jco.org on May 5, 2008.

Supported by GlaxoSmithKline R&D Limited.

Presented in part in posters at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL; 12th European Congress of Clinical Oncology, October 29-November 1, 2005, Paris, France; 28th Annual San Antonio Breast Cancer Symposium, December 8-11, 2005, San Antonio, TX; 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX; and 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on www.JCO.org.

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