A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck

Clin Cancer Res. 2012 Apr 15;18(8):2336-43. doi: 10.1158/1078-0432.CCR-11-2825. Epub 2012 Feb 27.

Abstract

Purpose: This study sought to determine the efficacy and safety profile of lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).

Experimental design: This phase II multiinstitutional study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those without (arm A) and those with (arm B) before exposure to an epidermal growth factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500 mg daily. Primary endpoints were response rate (arm A) and progression-free survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and survival pathways were assessed in paired tumor biopsies obtained before and after therapy.

Results: Forty-five patients were enrolled, 27 in arm A and 18 in arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients. Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1 vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial responses were observed, and stable disease was the best response observed in 41% of arm A (median duration, 50 days, range, 34-159) and 17% of arm B subjects (median, 163 days, range, 135-195). Median PFS was 52 days in both arms. Median OS was 288 (95% CI, 62-374) and 155 (95% CI, 75-242) days for arms A and B, respectively. Correlative analyses revealed an absence of EGFR inhibition in tumor tissue.

Conclusion: Lapatinib as a single agent in recurrent/metastatic SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor naive or refractory subjects.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Lapatinib
  • Male
  • Neoplasm Recurrence, Local / drug therapy
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects*
  • Quinazolines / therapeutic use
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Lapatinib
  • ErbB Receptors