Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study.

Abstract

PURPOSE:

This trial evaluated the efficacy of maintenance erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, after first-line chemotherapy.

PATIENTS AND METHODS:

Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian, primary peritoneal, or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first-line platinum-based chemotherapy (CT) and showed no signs of progression at the end of CT. Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation. EGFR immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutation analyses were performed in 318 patients.

RESULTS:

Between October 2005 and February 2008, 835 patients were randomly assigned (median follow-up, 51 months). Twenty-six percent of the patients stopped erlotinib as a result of adverse effects (of these, 67% were due to rash). For erlotinib and observation, respectively, the median progression-free survival was 12.7 and 12.4 months (hazard ratio [HR], 1.05; 95% CI, 0.90 to 1.23), and the median overall survival was 50.8 and 59.1 months (HR, 0.99; 95% CI, 0.81 to 1.20 months), respectively. No subgroup could be identified with improved effect of erlotinib, based on IHC or FISH for EGFR, or mutations in genes related to the EGFR pathway, or on rash during erlotinib therapy. However, patients with a positive FISH EGFR score had a worse overall survival (46.1 months) than those with a negative score (67.0 months; HR, 1.56; 95% CI, 1.01 to 2.40; P = .044). Global health/quality-of-life scores showed a significant difference during the first year (P = .0102) in favor of the observation arm.

CONCLUSION:

Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival.

• Authors: Ignace B Vergote, Antonio Jimeno, Florence Joly, Dionyssios Katsaros, Corneel Coens, Evelyn Despierre, Christian Marth, Marcia Hall, Christopher B Steer, Nicoletta Colombo, Anne Lesoin, Antonio Casado, Alexander Reinthaller, John Green, Martin Buck, Isabelle Ray-Coquard, Annamaria Ferrero, Laure Favier, Nick Simon Reed, Hervé Curé, Eric Pujade-Lauraine
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 4 Pg. 320-6 (Feb 01 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 24366937 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Platinum Compounds
• Protein Kinase Inhibitors
• Quinazolines
• Erlotinib Hydrochloride
• EGFR protein, human
• ErbB Receptors

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Ovarian Epithelial
• Disease-Free Survival
• Drug Administration Schedule
• Drug Eruptions (etiology)
• ErbB Receptors (genetics)
• Erlotinib Hydrochloride
• Europe
• Fallopian Tube Neoplasms (drug therapy, pathology)
• Female
• Follow-Up Studies
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Kaplan-Meier Estimate
• Maintenance Chemotherapy
• Middle Aged
• Mutation
• Neoplasm Staging
• Neoplasms, Glandular and Epithelial (drug therapy, pathology)
• Ovarian Neoplasms (drug therapy, pathology)
• Peritoneal Neoplasms (drug therapy, pathology)
• Platinum Compounds (administration & dosage)
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Quality of Life
• Quinazolines (administration & dosage, adverse effects)
• Signal Transduction (genetics)
• Watchful Waiting