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Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840.

Publication ,  Journal Article
Seidman, AD; Berry, D; Cirrincione, C; Harris, L; Muss, H; Marcom, PK; Gipson, G; Burstein, H; Lake, D; Shapiro, CL; Ungaro, P; Norton, L ...
Published in: J Clin Oncol
April 1, 2008

PURPOSE: Phase II trials suggested that weekly paclitaxel might be more effective and less toxic than every-3-weeks administration for metastatic breast cancer (MBC). Cancer and Leukemia Group B (CALGB) protocol 9840 was initiated to address this question. Subsequently trastuzumab was demonstrated to improve outcomes of paclitaxel therapy for human epidermal growth factor receptor-2 (HER-2)-positive patients, and was therefore incorporated. Because inhibition of HER-family signaling had potential efficacy even without HER-2 overexpression, we randomly assigned for trastuzumab in this population. PATIENTS AND METHODS: Patients were randomly assigned to paclitaxel 175 mg/m(2) every 3 weeks or 80 mg/m(2) weekly. After the first 171 patients, all HER-2-positive patients received trastuzumab; HER-2 nonoverexpressors were randomly assigned for trastuzumab, in addition to paclitaxel schedule. A total of 577 patients were treated on 9840. An additional 158 patients were included in analyses, for combined sample of 735. The primary end point was response rate (RR); secondary end points were time to progression (TTP), overall survival, and toxicity. Primary comparisons were between weekly versus every-3-weeks paclitaxel, and trastuzumab versus no trastuzumab in HER-2 nonoverexpressors. RESULTS: In the combined sample, weekly paclitaxel was superior to every-3-weeks administration: RR (42% v 29%, unadjusted odds ratio [OR] = 1.75; P = .0004), TTP (median, 9 v 5 months; adjusted HR = 1.43; P < .0001), and survival (median, 24 v 12 months; adjusted HR = 1.28; P = .0092). For HER-2 nonoverexpressors, trastuzumab did not improve efficacy. Grade 3 neuropathy was more common with weekly dosing (24% v 12%; P = .0003). CONCLUSION: Weekly paclitaxel is more effective than every-3-weeks administration for MBC. Trastuzumab did not improve efficacy for HER-2 nonoverexpressors. Neurotoxicity is a treatment-limiting toxicity for weekly paclitaxel.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

April 1, 2008

Volume

26

Issue

10

Start / End Page

1642 / 1649

Location

United States

Related Subject Headings

  • Trastuzumab
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Paclitaxel
  • Oncology & Carcinogenesis
  • Middle Aged
  • Kaplan-Meier Estimate
  • Humans
  • Female
  • Breast Neoplasms
 

Citation

APA
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MLA
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Seidman, Andrew D., Donald Berry, Constance Cirrincione, Lyndsay Harris, Hyman Muss, P Kelly Marcom, Grandella Gipson, et al. “Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840.J Clin Oncol 26, no. 10 (April 1, 2008): 1642–49. https://doi.org/10.1200/JCO.2007.11.6699.
Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642–1649.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

April 1, 2008

Volume

26

Issue

10

Start / End Page

1642 / 1649

Location

United States

Related Subject Headings

  • Trastuzumab
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Paclitaxel
  • Oncology & Carcinogenesis
  • Middle Aged
  • Kaplan-Meier Estimate
  • Humans
  • Female
  • Breast Neoplasms