Phase II study of lapatinib in combination with vinorelbine, as first or second-line therapy in women with HER2 overexpressing metastatic breast cancer

Helen Kent Chew, Lee Schwartzberg, Suprith Badarinath, Peter Rubin, Grace Shumaker, James Daugherty, Michelle DeSilvio, Janine Mahoney

Research output: Contribution to journalArticle

Abstract

Background Lapatinib in combination with capecitabine is approved for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress the human epidermal growth factor receptor 2 (HER2) and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Based on our phase I trial, we conducted a single arm, multicenter phase II study of lapatinib in combination with vinorelbine. Patient and methods Women with HER2-positive advanced breast cancer, who had received up to one prior regimen for metastatic disease, were eligible. Prior trastuzumab was allowed. Patients received daily lapatinib 1500 mg orally and vinorelbine 20 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Results Forty-four patients received the combination treatment, including 48% as second-line therapy. The ORR was 41% (95% confidence interval [CI] 26-55%), including 9% with a complete response. Median progression-free survival was 24.1 weeks (95% CI 17-37 weeks) and median duration of response was 32 weeks (95% CI 18-42 weeks). Nearly 80% of patients did not require a dose reduction in lapatinib, although most patients required one dose reduction of vinorelbine secondary to neutropenia. The most common toxicities were grade 1 and 2 diarrhea, nausea, fatigue and rash, and grade 3 and 4 neutropenia. One case of grade 3 asymptomatic decreased left ventricular ejection fraction event was reported. Conclusion The combination of lapatinib and vinorelbine was active, feasible and well tolerated in patients with HER2-positive advanced breast cancer.

Original languageEnglish (US)
JournalSpringerPlus
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Breast Neoplasms
Confidence Intervals
Neutropenia
Therapeutics
Anthracyclines
vinorelbine
human ERBB2 protein
lapatinib
Exanthema
Stroke Volume
Nausea
Disease-Free Survival
Fatigue
Diarrhea
Neoplasms
Trastuzumab

All Science Journal Classification (ASJC) codes

  • General

Cite this

Phase II study of lapatinib in combination with vinorelbine, as first or second-line therapy in women with HER2 overexpressing metastatic breast cancer. / Chew, Helen Kent; Schwartzberg, Lee; Badarinath, Suprith; Rubin, Peter; Shumaker, Grace; Daugherty, James; DeSilvio, Michelle; Mahoney, Janine.

In: SpringerPlus, Vol. 3, No. 1, 01.01.2014.

Research output: Contribution to journalArticle

Chew, Helen Kent ; Schwartzberg, Lee ; Badarinath, Suprith ; Rubin, Peter ; Shumaker, Grace ; Daugherty, James ; DeSilvio, Michelle ; Mahoney, Janine. / Phase II study of lapatinib in combination with vinorelbine, as first or second-line therapy in women with HER2 overexpressing metastatic breast cancer. In: SpringerPlus. 2014 ; Vol. 3, No. 1.
@article{666c0dad61d843a399a96d7e1bb5c453,
title = "Phase II study of lapatinib in combination with vinorelbine, as first or second-line therapy in women with HER2 overexpressing metastatic breast cancer",
abstract = "Background Lapatinib in combination with capecitabine is approved for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress the human epidermal growth factor receptor 2 (HER2) and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Based on our phase I trial, we conducted a single arm, multicenter phase II study of lapatinib in combination with vinorelbine. Patient and methods Women with HER2-positive advanced breast cancer, who had received up to one prior regimen for metastatic disease, were eligible. Prior trastuzumab was allowed. Patients received daily lapatinib 1500 mg orally and vinorelbine 20 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Results Forty-four patients received the combination treatment, including 48{\%} as second-line therapy. The ORR was 41{\%} (95{\%} confidence interval [CI] 26-55{\%}), including 9{\%} with a complete response. Median progression-free survival was 24.1 weeks (95{\%} CI 17-37 weeks) and median duration of response was 32 weeks (95{\%} CI 18-42 weeks). Nearly 80{\%} of patients did not require a dose reduction in lapatinib, although most patients required one dose reduction of vinorelbine secondary to neutropenia. The most common toxicities were grade 1 and 2 diarrhea, nausea, fatigue and rash, and grade 3 and 4 neutropenia. One case of grade 3 asymptomatic decreased left ventricular ejection fraction event was reported. Conclusion The combination of lapatinib and vinorelbine was active, feasible and well tolerated in patients with HER2-positive advanced breast cancer.",
author = "Chew, {Helen Kent} and Lee Schwartzberg and Suprith Badarinath and Peter Rubin and Grace Shumaker and James Daugherty and Michelle DeSilvio and Janine Mahoney",
year = "2014",
month = "1",
day = "1",
doi = "10.1186/2193-1801-3-108",
language = "English (US)",
volume = "3",
journal = "SpringerPlus",
issn = "2193-1801",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "1",

}

TY - JOUR

T1 - Phase II study of lapatinib in combination with vinorelbine, as first or second-line therapy in women with HER2 overexpressing metastatic breast cancer

AU - Chew, Helen Kent

AU - Schwartzberg, Lee

AU - Badarinath, Suprith

AU - Rubin, Peter

AU - Shumaker, Grace

AU - Daugherty, James

AU - DeSilvio, Michelle

AU - Mahoney, Janine

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background Lapatinib in combination with capecitabine is approved for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress the human epidermal growth factor receptor 2 (HER2) and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Based on our phase I trial, we conducted a single arm, multicenter phase II study of lapatinib in combination with vinorelbine. Patient and methods Women with HER2-positive advanced breast cancer, who had received up to one prior regimen for metastatic disease, were eligible. Prior trastuzumab was allowed. Patients received daily lapatinib 1500 mg orally and vinorelbine 20 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Results Forty-four patients received the combination treatment, including 48% as second-line therapy. The ORR was 41% (95% confidence interval [CI] 26-55%), including 9% with a complete response. Median progression-free survival was 24.1 weeks (95% CI 17-37 weeks) and median duration of response was 32 weeks (95% CI 18-42 weeks). Nearly 80% of patients did not require a dose reduction in lapatinib, although most patients required one dose reduction of vinorelbine secondary to neutropenia. The most common toxicities were grade 1 and 2 diarrhea, nausea, fatigue and rash, and grade 3 and 4 neutropenia. One case of grade 3 asymptomatic decreased left ventricular ejection fraction event was reported. Conclusion The combination of lapatinib and vinorelbine was active, feasible and well tolerated in patients with HER2-positive advanced breast cancer.

AB - Background Lapatinib in combination with capecitabine is approved for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress the human epidermal growth factor receptor 2 (HER2) and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Based on our phase I trial, we conducted a single arm, multicenter phase II study of lapatinib in combination with vinorelbine. Patient and methods Women with HER2-positive advanced breast cancer, who had received up to one prior regimen for metastatic disease, were eligible. Prior trastuzumab was allowed. Patients received daily lapatinib 1500 mg orally and vinorelbine 20 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Results Forty-four patients received the combination treatment, including 48% as second-line therapy. The ORR was 41% (95% confidence interval [CI] 26-55%), including 9% with a complete response. Median progression-free survival was 24.1 weeks (95% CI 17-37 weeks) and median duration of response was 32 weeks (95% CI 18-42 weeks). Nearly 80% of patients did not require a dose reduction in lapatinib, although most patients required one dose reduction of vinorelbine secondary to neutropenia. The most common toxicities were grade 1 and 2 diarrhea, nausea, fatigue and rash, and grade 3 and 4 neutropenia. One case of grade 3 asymptomatic decreased left ventricular ejection fraction event was reported. Conclusion The combination of lapatinib and vinorelbine was active, feasible and well tolerated in patients with HER2-positive advanced breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=84897752851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897752851&partnerID=8YFLogxK

U2 - 10.1186/2193-1801-3-108

DO - 10.1186/2193-1801-3-108

M3 - Article

VL - 3

JO - SpringerPlus

JF - SpringerPlus

SN - 2193-1801

IS - 1

ER -