Anopen-label safety study of lapatinib plus trastuzumab plus paclitaxel in first-line HER2-positive metastatic breast cancer

Francisco J. Esteva, Sandra X. Franco, Maura K. Hagan, Abenaa M. Brewster, Robert A. Somer, Will Williams, Allison M. Florance, Simon Turner, Steven Stein, Alejandra Perez

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background. Recent data support the hypothesis that combining lapatinib and trastuzumab with taxane chemotherapy may offer added clinical benefit to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study examined the safety of the triplet combination in first-line HER2-positive MBC. Patients and Methods. Patients were enrolled into three sequential cohorts; the last two cohorts were added by protocol amendmentfollowing review of safety data from cohort 1. Patients in cohort 1 received lapatinib (1000 mg/day) plus paclitaxel (80 mg/m2 per week, 3 of every 4 weeks); cohort 2 received lapatinib (1000 mg/day) plus paclitaxel (70 mg/m2 per week, 3 of every 4 weeks); and cohort 3 received lapatinib (750 mg/day) plus paclitaxel (80mg/m2 per week, 3 of every 4 weeks). All received standard trastuzumab dosing. The primary objective was assessment of dose-limiting toxicities, safety, and tolerability of this combination. Results. The most frequent adverse events (AEs) for all cohorts were diarrhea (89%), rash (79%), fatigue (73%), alopecia (63%), nausea (63%), and vomiting (40%). In cohorts 1 and 2, the incidence of grade 3 diarrhea was 62% and 50%, respectively; in cohort 3, the incidence was 25% (with prophylactic loperamide). Dehydration was the most frequent serious AE (10%). Across cohorts, overall response rate was 75%. Conclusions. The dose-limiting toxicity of paclitaxel, trastuzumab, and lapatinib in first-line HER2-positiveMBCwas diarrhea. Of the triplet combinations tested, the cohort receiving 750 mg/day dose of lapatinib had the lowest incidence of diarrhea; therefore, this dose should be used in further studies on the treatment of MBC.

Original languageEnglish (US)
Pages (from-to)661-666
Number of pages6
JournalOncologist
Volume18
Issue number6
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Paclitaxel
Breast Neoplasms
Safety
Diarrhea
Incidence
Loperamide
Alopecia
Exanthema
Dehydration
Nausea
Vomiting
Fatigue
Trastuzumab
human ERBB2 protein
lapatinib
Drug Therapy

Keywords

  • Breast cancer
  • HER2
  • Lapatinib
  • Paclitaxel
  • Trastuzumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Anopen-label safety study of lapatinib plus trastuzumab plus paclitaxel in first-line HER2-positive metastatic breast cancer. / Esteva, Francisco J.; Franco, Sandra X.; Hagan, Maura K.; Brewster, Abenaa M.; Somer, Robert A.; Williams, Will; Florance, Allison M.; Turner, Simon; Stein, Steven; Perez, Alejandra.

In: Oncologist, Vol. 18, No. 6, 2013, p. 661-666.

Research output: Contribution to journalArticle

Esteva, FJ, Franco, SX, Hagan, MK, Brewster, AM, Somer, RA, Williams, W, Florance, AM, Turner, S, Stein, S & Perez, A 2013, 'Anopen-label safety study of lapatinib plus trastuzumab plus paclitaxel in first-line HER2-positive metastatic breast cancer', Oncologist, vol. 18, no. 6, pp. 661-666. https://doi.org/10.1634/theoncologist.2012-0129
Esteva, Francisco J. ; Franco, Sandra X. ; Hagan, Maura K. ; Brewster, Abenaa M. ; Somer, Robert A. ; Williams, Will ; Florance, Allison M. ; Turner, Simon ; Stein, Steven ; Perez, Alejandra. / Anopen-label safety study of lapatinib plus trastuzumab plus paclitaxel in first-line HER2-positive metastatic breast cancer. In: Oncologist. 2013 ; Vol. 18, No. 6. pp. 661-666.
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abstract = "Background. Recent data support the hypothesis that combining lapatinib and trastuzumab with taxane chemotherapy may offer added clinical benefit to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study examined the safety of the triplet combination in first-line HER2-positive MBC. Patients and Methods. Patients were enrolled into three sequential cohorts; the last two cohorts were added by protocol amendmentfollowing review of safety data from cohort 1. Patients in cohort 1 received lapatinib (1000 mg/day) plus paclitaxel (80 mg/m2 per week, 3 of every 4 weeks); cohort 2 received lapatinib (1000 mg/day) plus paclitaxel (70 mg/m2 per week, 3 of every 4 weeks); and cohort 3 received lapatinib (750 mg/day) plus paclitaxel (80mg/m2 per week, 3 of every 4 weeks). All received standard trastuzumab dosing. The primary objective was assessment of dose-limiting toxicities, safety, and tolerability of this combination. Results. The most frequent adverse events (AEs) for all cohorts were diarrhea (89{\%}), rash (79{\%}), fatigue (73{\%}), alopecia (63{\%}), nausea (63{\%}), and vomiting (40{\%}). In cohorts 1 and 2, the incidence of grade 3 diarrhea was 62{\%} and 50{\%}, respectively; in cohort 3, the incidence was 25{\%} (with prophylactic loperamide). Dehydration was the most frequent serious AE (10{\%}). Across cohorts, overall response rate was 75{\%}. Conclusions. The dose-limiting toxicity of paclitaxel, trastuzumab, and lapatinib in first-line HER2-positiveMBCwas diarrhea. Of the triplet combinations tested, the cohort receiving 750 mg/day dose of lapatinib had the lowest incidence of diarrhea; therefore, this dose should be used in further studies on the treatment of MBC.",
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AU - Brewster, Abenaa M.

AU - Somer, Robert A.

AU - Williams, Will

AU - Florance, Allison M.

AU - Turner, Simon

AU - Stein, Steven

AU - Perez, Alejandra

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AB - Background. Recent data support the hypothesis that combining lapatinib and trastuzumab with taxane chemotherapy may offer added clinical benefit to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study examined the safety of the triplet combination in first-line HER2-positive MBC. Patients and Methods. Patients were enrolled into three sequential cohorts; the last two cohorts were added by protocol amendmentfollowing review of safety data from cohort 1. Patients in cohort 1 received lapatinib (1000 mg/day) plus paclitaxel (80 mg/m2 per week, 3 of every 4 weeks); cohort 2 received lapatinib (1000 mg/day) plus paclitaxel (70 mg/m2 per week, 3 of every 4 weeks); and cohort 3 received lapatinib (750 mg/day) plus paclitaxel (80mg/m2 per week, 3 of every 4 weeks). All received standard trastuzumab dosing. The primary objective was assessment of dose-limiting toxicities, safety, and tolerability of this combination. Results. The most frequent adverse events (AEs) for all cohorts were diarrhea (89%), rash (79%), fatigue (73%), alopecia (63%), nausea (63%), and vomiting (40%). In cohorts 1 and 2, the incidence of grade 3 diarrhea was 62% and 50%, respectively; in cohort 3, the incidence was 25% (with prophylactic loperamide). Dehydration was the most frequent serious AE (10%). Across cohorts, overall response rate was 75%. Conclusions. The dose-limiting toxicity of paclitaxel, trastuzumab, and lapatinib in first-line HER2-positiveMBCwas diarrhea. Of the triplet combinations tested, the cohort receiving 750 mg/day dose of lapatinib had the lowest incidence of diarrhea; therefore, this dose should be used in further studies on the treatment of MBC.

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