Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2+ metastatic breast cancer

Mohammad Jahanzeb, Joanne E. Mortimer, Furhan Yunus, David H. Irwin, James Speyer, Alan J. Koletsky, Paula Klein, Tariq Sabir, Lori Kronish

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Purpose. Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab. Patients and Methods. A phase II, open-label trial of intravenous vinorelbine (30 mg/m2 on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2+ metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events. Results. Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78% (29/37, 95% confidence interval [CI] 62%-90%), including four (11%, 95% CI 3%-25%) complete and 25 (68%) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3+ = 82 % (18/22) response and IHC 2+ = 58% (7/12) response. Median time to progression was 72 weeks (95% CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9% of courses) and omissions (10% of courses). No patient experienced serious cardiac toxicity. Conclusions. Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2+ metastatic breast cancer. Further investigation of this novel regimen is planned.

Original languageEnglish
Pages (from-to)410-417
Number of pages8
JournalOncologist
Volume7
Issue number5
DOIs
StatePublished - Nov 14 2002
Externally publishedYes

Fingerprint

Breast Neoplasms
Confidence Intervals
Neutropenia
Therapeutics
Immunohistochemistry
vinorelbine
Trastuzumab
human ERBB2 protein
Disease Progression
Drug Therapy
Survival
Neoplasms

Keywords

  • Breast neoplasms
  • Fluorescence
  • Immunohistochemistry
  • In situ hybridization
  • Neutropenia

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2+ metastatic breast cancer. / Jahanzeb, Mohammad; Mortimer, Joanne E.; Yunus, Furhan; Irwin, David H.; Speyer, James; Koletsky, Alan J.; Klein, Paula; Sabir, Tariq; Kronish, Lori.

In: Oncologist, Vol. 7, No. 5, 14.11.2002, p. 410-417.

Research output: Contribution to journalArticle

Jahanzeb, M, Mortimer, JE, Yunus, F, Irwin, DH, Speyer, J, Koletsky, AJ, Klein, P, Sabir, T & Kronish, L 2002, 'Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2+ metastatic breast cancer', Oncologist, vol. 7, no. 5, pp. 410-417. https://doi.org/10.1634/theoncologist.7-5-410
Jahanzeb, Mohammad ; Mortimer, Joanne E. ; Yunus, Furhan ; Irwin, David H. ; Speyer, James ; Koletsky, Alan J. ; Klein, Paula ; Sabir, Tariq ; Kronish, Lori. / Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2+ metastatic breast cancer. In: Oncologist. 2002 ; Vol. 7, No. 5. pp. 410-417.
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abstract = "Purpose. Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab. Patients and Methods. A phase II, open-label trial of intravenous vinorelbine (30 mg/m2 on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2+ metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events. Results. Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78{\%} (29/37, 95{\%} confidence interval [CI] 62{\%}-90{\%}), including four (11{\%}, 95{\%} CI 3{\%}-25{\%}) complete and 25 (68{\%}) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3+ = 82 {\%} (18/22) response and IHC 2+ = 58{\%} (7/12) response. Median time to progression was 72 weeks (95{\%} CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9{\%} of courses) and omissions (10{\%} of courses). No patient experienced serious cardiac toxicity. Conclusions. Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2+ metastatic breast cancer. Further investigation of this novel regimen is planned.",
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T1 - Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2+ metastatic breast cancer

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AU - Mortimer, Joanne E.

AU - Yunus, Furhan

AU - Irwin, David H.

AU - Speyer, James

AU - Koletsky, Alan J.

AU - Klein, Paula

AU - Sabir, Tariq

AU - Kronish, Lori

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N2 - Purpose. Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab. Patients and Methods. A phase II, open-label trial of intravenous vinorelbine (30 mg/m2 on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2+ metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events. Results. Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78% (29/37, 95% confidence interval [CI] 62%-90%), including four (11%, 95% CI 3%-25%) complete and 25 (68%) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3+ = 82 % (18/22) response and IHC 2+ = 58% (7/12) response. Median time to progression was 72 weeks (95% CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9% of courses) and omissions (10% of courses). No patient experienced serious cardiac toxicity. Conclusions. Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2+ metastatic breast cancer. Further investigation of this novel regimen is planned.

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