A phase II evaluation of lapatinib in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a gynecologic oncology group study

Gynecol Oncol. 2012 Mar;124(3):569-74. doi: 10.1016/j.ygyno.2011.10.022. Epub 2011 Oct 28.

Abstract

Objective: Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer. We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations.

Methods: Eligible patients had recurrent or persistent EOC or primary peritoneal carcinoma, measurable disease, and up to 2 prior chemotherapy regimens for recurrent disease. Patients were treated with lapatinib 1500 mg/day. The primary endpoint of efficacy was 6-month progression free survival (PFS).

Results: Twenty-five of 28 patients were eligible and evaluable for analysis of efficacy and toxicity. Two (8.0%) were alive and progression-free at 6 months. No objective responses were observed. There were 1 grade 4 toxicity (fatigue) and few grade 3 toxicities. Associations between Ki-67 with prior platinum-free interval, PFS, and a polymorphism in EGFR were suggested.

Conclusions: Lapatinib has minimal activity in recurrent ovarian cancer. Ki-67 expression may be associated with prior PFS and a polymorphism in EGFR exon 20 (2361G>A, Q787Q).

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Ki-67 Antigen / biosynthesis
  • Lapatinib
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / metabolism
  • Polymorphism, Genetic
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*

Substances

  • Antineoplastic Agents
  • Ki-67 Antigen
  • Quinazolines
  • Lapatinib
  • ErbB Receptors