Maintenance erlotinib after first-line treatment in ovarian cancer does not improve progression-free survival versus observation alone

EORTC trial 55041 results show that maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free survival. This trial, a randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first line platinum-based chemotherapy for ovarian carcinoma, was conducted by the EORTC Gynecological Cancer Group in cooperation with GINECO (Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens), AGO (Arbeitsgemeinschaft Gynäkologische Onkologie), MRC (Medical Research Council), ANZGOG (Australia New Zealand Gynaecological Oncology Group) and MaNGO (Mario Negri Gynecologic Oncology) under the EORTC (European Organisation for Research and Treatment of Cancer) Intergroup policies.

The trial was designed to determine whether patients with ovarian cancer who had no evidence of disease progression would benefit from maintenance treatment with erlotinib following first line platinum-based chemotherapy (for 6-9 cycles) compared to observation (the current standard). Since most ovarian cancer patients achieve stable disease after first line treatment, but disease ultimately recurs, it was important to determine whether administration of erlotinib as a maintenance treatment might extend the time until disease recurrence and/or death (i.e. progression-free survival) in these patients.

In 125 institutions located in ten countries, 835 patients with high-risk FIGO stage I or stage II-IV epithelial ovarian, primary peritoneal or fallopian tube cancer were randomized to erlotinib (420 patients) and Observation (415 patients) arms. Patients in both arms received first line platinum-based chemotherapy and exhibited no signs of progression at the end of chemotherapy. Patients in the erlotinib arm received maintenance erlotinib (150 mg orally once daily) for the following two years, while those patients in the observation arm received no further treatment.

Progression-free survival was 12.7 months for the erlotinib arm and 12.4 months for the Observation arm (hazard ratio [HR] = 1.05, confidence interval [CI] 0.90, 1.23; p = 0.525). Progression-free survival, the primary endpoint, was determined by RECIST in combination with Gynecological Cancer Intergroup CA125 criteria, and the median follow-up was 51 months. Overall survival was 50.8 months for the erlotinib arm and 59.4 months for the Observation arm (HR = 0.99, CI 0.81, 1.20; p = 0.903). Due to well characterized side effects, primarily rash, 26% of the patients in the erlotinib arm stopped maintenance treatment with erlotinib before the end of the two year treatment period.

Professor Ignace Vergote, University Hospitals Leuven, notes that “this trial was the first randomized phase III trial in first line ovarian cancer using a molecularly targeted agent. 835 patients were randomized by the EORTC Gynecological Cancer Group and cooperating national groups, and the time of accrual was shorter than anticipated. Unfortunately, maintenance erlotinib did not improve progression-free survival in the general population. Still, there is further interest in exploring the effects of erlotinib in certain subgroups for future insights. These subgroups might be isolated by ongoing translational research concerning the epidermal growth factor receptor (EGFR) and related pathways in patients’ tumors.”

About ovarian cancer

Ovarian cancer is a major cause of cancer-related death in women, and over 75% of patients present at an advanced stage. The standard chemotherapy regimen for patients with advanced ovarian cancer is the platinum-based chemotherapy, a combination of paclitaxel and carboplatin. Despite initial response to first line platinum-based chemotherapy, most patients relapse and die of their disease.

About Tarceva (erlotinib)

Tarceva is a once-daily, oral, non-chemotherapy treatment currently licensed for the treatment of advanced or metastatic NSCLC and locally advanced, unresectable or metastatic pancreatic cancer. It has been shown to potently inhibit EGFR, a protein involved in the growth and development of cancers. Tarceva is a trademark of OSI Pharmaceuticals, LLC, a wholly owned subsidiary of Astellas Holding US Inc. a holding company owned by Astellas Pharma Inc. Tarceva is developed and commercialized by OSI in partnership with Genentech in the United States, Chugai in Japan and Roche in the rest of the world.

About the EORTC

The EORTC is a unique organization – a vibrant example of the fact that academic science and research know no national boundaries. Established in 1962, the EORTC is a non-profit European research organization operating as an international association under Belgian law. The EORTC currently links a network of more than 2,500 pre-clinical scientists and oncologists in more than 300 hospitals in over 30 countries. It encompasses all aspects of cancer research, from translational research and new drug development to large phase III clinical trials and meta-analyses. The 170 members of the EORTC Headquarters staff handle some 6,000 new patients enrolled each year in cancer clinical trials, approximately 30 protocols that are permanently open to patient entry, over 50,000 patients who are in follow-up, and a database of more than 180,000 patients. The ultimate goal of the EORTC is to improve the future of cancer therapy by developing new agents and innovative approaches and to test more effective treatment strategies using commercially available drugs, or surgery and radiotherapy.

John Bean