NE Oncology Issue – September 2011

Background

In 2006, the Gynecologic Cancer InterGroup (GCIG) ICON7 study — a multicenter, phase III randomized trial — was launched and designed to investigate the safety and efficacy of adding bevacizumab to standard chemotherapy in women with newly diagnosed ovarian cancer.

Results presented at the European Society for Medical Oncology (ESMO) 2010 meeting of bevacizumab combined with standard carboplatin (C) and paclitaxel (P) followed by continued single-agent bevacizumab demonstrated a benefit in progression-free survival (PFS) and suggested a trend for overall survival (OS) improvement, but results were immature (only 34% of the events required for final OS analysis).1

At ASCO 2011, Kristensen and colleagues presented interim results of this trial. The analyses of mature PFS data suggest a PFS benefit from bevacizumab, and a trend toward OS.2 Furthermore, a subgroup analysis of poor prognosis patients was performed in an exploratory manner.

The final analysis of OS will be performed when 715 deaths have occurred (with results expected in 2013).

Study design

  • In the ICON7 study, eligible women with newly diagnosed or advanced epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC) were randomized in a one-to-one fashion to six cycles of thrice-weekly chemotherapy (carboplatin [C] area under the curve[AUC] 5 or 6 and paclitaxel [P] 175 mg/m2) alone, or the same chemotherapy given concurrently with bevacizumab (7.5 mg/kg) every three weeks, for a total duration of 12 months.
  • Five or six cycles of this protocol were followed by continued thrice-weekly single-agent bevacizumab for 12 additional cycles, or until progression (whichever occurred first).
  • Early disease was defined as International Federation of Gynecology and Obstetrics (FIGO) stage I or IIa (grade 3 or clear cell), capped ≤10%; advanced disease was defined as stage IIb-IV.
  • The primary endpoint of the trial was PFS; OS was the secondary endpoint.

Key findings

  • From December 2006 to February 2009, 1,528 women were randomized from 263 centres in seven GCIG groups.
  • Baseline characteristics were balanced between study arms: median age (57 years); most patients had serous histology (69%); high-risk early-stage disease (9%); highrisk/ poor prognosis patients (30%).
  • The mature PFS analysis had a median follow-up period of 19 months (cut-off November 2010).
  • The gain in median PFS was 2.4 months, with the curves merging after two years.
  • The median PFS in the bevacizumab arm was 19.8 months, versus 17.4 months in the control arm (HR = 0.87 [95% CI = 0.77–0.99], p = 0.039). (Figure 1)
  • OS in the high-risk group (stage III with >1 cm after debulking, or stage IV with debulking) showed a clear difference in treatment effect:
    • 47% of patients in the control arm have died versus 34% in the bevacizumab group (HR = 0.64; 36% reduction in the risk of death);
    • The gain in median OS was approximately eight months (p = 0.002). (Figure 2)
  • By risk group, there was a clear difference in OS effect in the high-risk group versus the other patient groups (where at present, no difference in OS has been seen) although the data are immature (median OS not yet reached, p = 0.64, HR = 1.07; final analyses expected in two years).

Key conclusions

  • The overall trend for improvement in OS from bevacizumab continued with a numerically larger benefit in poor prognosis patients.
  • Interim survival data from this randomized phase III trial suggest that adding bevacizumab to standard C plus P chemotherapy for the treatment of newly diagnosed ovarian cancer may offer benefit over treatment with chemotherapy alone, particularly in patients with more aggressive disease.
  • Bevacizumab combined with chemotherapy and continued alone (7.5 mg/kg for 12 months) versus chemotherapy demonstrated continued improvement in PFS, and a trend for improved OS continued in the total population.
  • The treatment effect of adding bevacizumab to standard chemotherapy was greater in high-risk patients.
  • Final OS results for this study are expected in 2013.

References: 1. Perren T, Swart AM, Pfistere J, et al. ICON7: A phase III Randomised Gynaecologic Cancer InterGroup (GCIG) trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab in women with newly diagnosed epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC). ESMO 2010 (Abstract LBA4). 2. Kristensen G, Perren T, Qian W, et al. Result of interim analysis of overall survival in the GCIG ICON7 phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. J Clin Oncol (ASCO Annual Meeting Abstracts) 2011;29: LBA5006.

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Canadian Perspectives

dr-lachance
Silvy Lachance, MD, FRCPC, CSPQ
Dr. Silvy Lachance is currently a hematologist, clinical researcher, and Director of the Stem Cell Transplant Program at the MaisonneuveRosement Hospital in Montreal, Quebec, and Professor of Medicine and Director of the Fellowship Program in Stem Cell Transplantation at the University of Montreal. In 1995, Dr. Lachance established the first Stem Cell Transplant Unit at the University Health Centre (CUSE) in Sherbrooke, Quebec. She joined the Hematology and Oncology Division of the Montreal General Hospital as a transplant physician in 1997 and became an Associate Professor of Medicine at McGill University in 2005, holding both positions until 2006. Dr. Lachance has served as chair of the Continuing Medical Education Committee of the Quebec Association of Hematologists and Oncologists, and is currently treasurer of the executive committee. She has also served as chair of the jury for the hematology specialty exam board of the Collège des Médecins du Québec (CMQ). Her research interests include stem cell transplant, graft-versus-host-disease, and lymphoproliferative disorders.

dr-petrella
Teresa Petrella, BSc, MD, MSc, FRCPC
Teresa Petrella is a Medical Oncologist at the Odette Cancer Centre (OCC) in Toronto, Canada and an Assistant Professor at the University of Toronto. Dr. Petrella has a BSc in Molecular Biology from the University of Western Ontario and she completed her MD at Queen’s University. Her Internal Medicine and Medical Oncology training was at McMaster University. She subsequently completed a fellowship in Melanoma and Breast Cancer at the Toronto Sunnybrook Regional Cancer Centre along with a Masters degree in Health Research Methodology at McMaster University. She was the recipient of a CIHR/CAMO award for her research in vaccine therapy in combination with interferon for melanoma patients. Dr. Petrella joined the staff at OCC in 2002 and became the head of the Melanoma Site Group. She also chairs the Provincial Guidelines Melanoma Disease Site Group Program in Evidence Based Care the National Cancer Institute of Canada (NCIC) Melanoma Clinical Trials Group. Her research interests are in melanoma and breast cancer and she is currently the Principal Investigator for several multicentre trials investigating novel therapies in melanoma.