341P - Adjusted indirect comparison analysis demonstrates significant benefit in progression-free survival for fulvestrant 500mg compared to anastrozole in...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Peter Schmid
Authors P. Schmid1, P. Turner2, M. Howlett3
  • 1Medical Oncology, Brighton and Sussex Medical School, BN1 9PX - Brighton/UK
  • 2Payer Evidence, AstraZeneca Ltd, LU1 3LU - Luton/UK
  • 3Medical Affairs, Astrazeneca Ltd, LU1 3LU - Luton/UK

Abstract

Objectives

Randomised controlled trials (RCTs) provide the highest level of evidence for comparing two treatments. However, with the increasing number of cancer drugs, direct comparison through RCTs is not feasible for all treatment indications and combinations. Bucher et al (1997) have developed a method for an adjusted indirect comparison analysis between RCTs. This method was used to compare the efficacy of fulvestrant 500mg and anastrozole 1mg in advanced breast cancer (ABC).

Methods

A systematic literature search on RCTs of fulvestrant 500mg or anastrozole 1mg in ABC was performed in June 2011, using CENTRAL, EMBASE and MEDLINE databases. Published data were used to perform a meta-analysis and an adjusted indirect comparison analysis (Bucher method). The primary endpoint was progression free survival (PFS).

Results

Three RCTs with 1023 patients were identified comparing fulvestrant 500mg (F500) with fulvestrant 250mg (F250), and two RCTs with a total of 851 patients were identified comparing anastrozole 1mg (Ana) with fulvestrant 250mg. Meta-analysis demonstrated a significant benefit in PFS for F500 compared to F250 (Hazard ratio (HR) 0.80 95% Confidence Interval (CI):0.69-0.93). There was no significant difference in PFS between Ana and F250 (HR 0.95, 95%CI 0.82-1.1). Using F250 as common comparator, the adjusted indirect comparison analysis demonstrated a significant benefit in PFS for F500 compared to Ana (HR 0.76, 95%CI 0.62-0.94).

Conclusions

In the absence of a direct RCT comparison, this adjusted indirect comparison shows that fulvestrant 500mg significantly improves PFS in ABC compared to anastrozole 1mg. Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997). The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997 Jun;50(6):683-91.

Disclosure

P. Turner: Pauline Turner is a full-time employee of AstraZeneca and is a stockholder in Astra Zeneca.

M. Howlett: Matthew Howlett is a full time employee of Astrazeneca and is a stockholder in Astrazeneca.

All other authors have declared no conflicts of interest.