328PD - Progression-free survival as a surrogate for overall survival in metastatic breast cancer

Date 01 October 2012
Event ESMO Congress 2012
Session Breast cancer, locally advanced and metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Catherine Beauchemin
Authors C. Beauchemin1, D. Cooper2, M. Lapierre3, L. Yelle4, J. Lachaine3
  • 1Faculty Of Pharmacy, University of Montreal, H3C3J7 - Montreal/CA
  • 2Direction Scientifique De L'inscription, Institut national d’excellence en santé et en services sociaux (INESSS), Quebec/CA
  • 3Faculty Of Pharmacy, University of Montreal, Montreal/CA
  • 4Oncology Department, Notre-Dame Hospital, Montreal/CA

Abstract

Objectives

Progression-free survival (PFS) is frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS for overall survival (OS) remains a matter of uncertainty in metastatic breast cancer (mBC). Therefore, the aim of this study was to assess the relationship between PFS and OS in mBC using a trial-based approach.

Methods

A systematic literature review was conducted using the PICO method: Population consisted of women with mBC; Interventions and Comparators were standard treatments for mBC or best supportive care; Outcomes of interest were median PFS or TTP and median OS. A correlation analysis between median PFS and OS was first performed and subgroup analyses were conducted to explore possible reasons for heterogeneity. Then, the relationship between the treatment effect on PFS and OS was assessed. The treatment effect on PFS and OS was quantified by the absolute difference of median values. Linear regression analysis was also conducted to predict the effects of a new anticancer drug on OS on the basis of its effects on PFS.

Results

A total of 5041 studies were identified and 144 fulfilled the eligibility criteria. Selected studies included 315 treatment arms, which represents 43,459 patients with mBC. There was a significant relationship between median PFS and median OS across included trials (r = 0.428; p < 0.01). The correlation between median PFS/TTP and median OS was higher for studies evaluating chemotherapy alone (r = 0.575; p ≤ 0.01) or in combination (r = 0.632; p ≤ 0.01) compared with those evaluating hormone therapy (non-significant r). The correlation coefficient for the treatment effect on PFS and OS was estimated at 0.427 (p < 0.01). The linear regression equation was: ΔOS = -0.088 (95% CI, -1.347 to 1.172) + 1.753 (95% CI, 1.307 to 2.198) * ΔPFS, with a proportion of variation explained (R2) of 0.86. Results of the regression analysis predict that a difference in median PFS/TTP of 5, 10, 15, and 20 months would translate into a difference in median OS of 8.7, 17.4, 26.2, and 35.0 months respectively.

Conclusion

The present findings point toward a statistically significant correlation between PFS and OS in the context of mBC and support the surrogacy of PFS for OS in this cancer setting.

Disclosure

All authors have declared no conflicts of interest.