Randomized phase II study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer

J Clin Oncol. 2013 Jul 10;31(20):2586-92. doi: 10.1200/JCO.2012.46.2408. Epub 2013 Jun 3.

Abstract

Purpose: Epidermal growth factor receptor is overexpressed in metastatic triple-negative breast cancers (mTNBCs), an aggressive subtype of breast cancer. Our randomized phase II study investigated cisplatin with or without cetuximab in this setting.

Patients and methods: Patients who had received no more than one previous chemotherapy regimen were randomly assigned on a 2:1 schedule to receive no more than six cycles of cisplatin plus cetuximab or cisplatin alone. Patients receiving cisplatin alone could switch to cisplatin plus cetuximab or cetuximab alone on disease progression. The primary end point was overall response rate (ORR). Secondary end points studied included progression-free survival (PFS), overall survival (OS), and safety profiles. Analyses included a significance level of α = .10 with no adjustments for multiplicity.

Results: The full analysis set comprised 115 patients receiving cisplatin plus cetuximab and 58 receiving cisplatin alone; 31 patients whose disease progressed on cisplatin alone switched to cetuximab-containing therapy. The ORR was 20% (95% CI, 13 to 29) with cisplatin plus cetuximab and 10% (95% CI, 4 to 21) with cisplatin alone (odds ratio, 2.13; 95% CI, 0.81 to 5.59; P = .11). Cisplatin plus cetuximab resulted in longer PFS compared with cisplatin alone (median, 3.7 v 1.5 months; hazard ratio [HR], 0.67; 95% CI, 0.47 to 0.97; P = .032). Corresponding median OS was 12.9 versus 9.4 months (HR, 0.82; 95% CI, 0.56 to 1.20; P = .31). Common grade 3/4 adverse events included acne-like rash, neutropenia, and fatigue.

Conclusion: While the primary study end point was not met, adding cetuximab to cisplatin doubled the ORR and appeared to prolong PFS and OS, warranting further investigation in mTNBC.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cetuximab
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Confidence Intervals
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • ErbB Receptors / drug effects
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Maximum Tolerated Dose
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / drug effects
  • Receptors, Progesterone / metabolism
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ErbB Receptors
  • Cetuximab
  • Cisplatin