N0436 (Alliance): A Phase II Trial of Irinotecan With Cetuximab in Patients With Metastatic Breast Cancer Previously Exposed to Anthracycline and/or Taxane-Containing Therapy

Clin Breast Cancer. 2016 Feb;16(1):23-30. doi: 10.1016/j.clbc.2015.08.002. Epub 2015 Aug 19.

Abstract

Background: Irinotecan has a 20% to 25% response rate (RR) in patients with previously treated metastatic breast cancer (MBC). Epidermal growth factor receptor (EGFR) is overexpressed in some MBC, especially in triple-negative breast cancer (TNBC). Cetuximab is a monoclonal antibody against EGFR with additive preclinical activity with irinotecan.

Patients and methods: We report a 1-stage phase II study on MBC, measurable disease, and previous anthracycline and/or taxane therapy. Patients received cetuximab 400 mg/m(2) on day 1 cycle 1 then 250 mg/m(2) weekly thereafter and irinotecan 80 mg/m(2) on days 1 and 8 of each 21-day cycle. The primary end point was overall RR (ORR) according to Response Evaluation Criteria in Solid Tumors criteria (version 1.1).

Results: Of 19 eligible patients enrolled from February to September 2006, 14 patients (74%) had visceral disease, seven patients (37%) were hormone receptor-positive, two patients (11%) HER2-positive, and 11 patients (58%) were triple-negative. Patients received a median of 2 cycles (range, 1-37). Confirmed ORR was 11% (95% confidence interval [CI], 1%-33%), with 1 partial response and 1 complete response. One patient had stable disease for 8 months. RR for TNBC versus non-TNBC was 18% versus 0% (P = .49). Median time to progression was 1.4 months (95% CI, 1.0-2.2) and median overall survival was 9.4 months (95% CI, 2.8-16.1). Twelve patients had disease progression within 2 cycles during therapy. Because of a low RR and rapid disease progression, the study leadership decided to close the trial early.

Conclusion: The tolerability of the combination of cetuximab and irinotecan is acceptable but demonstrated low overall activity. Potentially promising results were noted in patients with TNBC and further studies of these patients might be considered.

Keywords: EGFR; Refractory Treatment; Targeted Therapy; Triple Negative.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Cetuximab / administration & dosage
  • Cetuximab / adverse effects
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Irinotecan
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Metastasis
  • Salvage Therapy / methods*
  • Taxoids / therapeutic use

Substances

  • Anthracyclines
  • Taxoids
  • Irinotecan
  • Cetuximab
  • Camptothecin