A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI - PubMed (original) (raw)

A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI

Ian Chau et al. BMC Cancer. 2014.

Abstract

Background: The VELOUR study demonstrated a survival benefit for FOLFIRI + aflibercept versus FOLFIRI + placebo in metastatic colorectal cancer (mCRC) patients who progressed on oxaliplatin-based chemotherapy. Continued divergence of overall survival (OS) curves in the intension to treat (ITT) population, with the survival advantage persisting beyond median survival time, suggested subpopulations might have different magnitudes of survival gain. Additionally, 10% of patients within VELOUR had recurrence during or within 6 months of completing oxaliplatin-based adjuvant therapy (adjuvant fast relapsers)--previously identified as having poorer survival outcomes.

Methods: To determine which patients received the greatest benefit from FOLFIRI-aflibercept, a post hoc multivariate analysis of the VELOUR ITT population was conducted. Prognostic factors identified were applied to the ITT population, excluding adjuvant fast relapsers, to derive OS prognostic profiles.

Results: The better efficacy subgroup was identified as patients within VELOUR exclusive of adjuvant fast relapsers and had performance status (PS) 0 with any number of metastatic site or PS 1 with <2 metastatic site. A significant improvement in efficacy outcome was observed with aflibercept in the better efficacy subgroup. Median OS for FOLFIRI-aflibercept and FOLFIRI-placebo:16.2 and 13.1 months (adjusted Hazard Ratio [HR] = 0.73; 95% confidence interval [CI]: 0.61-0.86); median progression free survival (PFS): 7.2 and 4.8 months (adjusted HR = 0.68; 95% CI: 0.57-0.80); and objective response rate (ORR): 24% versus 11% respectively. Poorer efficacy subgroup comprised of adjuvant fast relapsers or patients with PS2 or PS1 with ≥ 2 metastatic sites. In poorer efficacy subgroup, no benefit was seen with aflibercept. Median OS for FOLFIRI-aflibercept and FOLFIRI-placebo: 10.4 and 9.6 months (adjusted HR = 0.97; 95% CI: 0.78-1.21) respectively with no improvement in PFS or ORR.

Conclusion: This analysis suggests that within VELOUR, patients in the better efficacy subgroup may derive enhanced benefit from treatment with FOLFIRI-aflibercept. These prognostic criteria may guide practitioners toward optimal use of targeted biologicals in appropriate second-line mCRC patients.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Construction of the prognostic profile for the better efficacy subgroup. ECOG: European Cooperative Oncology Group; OS: overall survival; PS: Performance Status; ITT: Intention to Treat.

Figure 2

Figure 2

Overall survival according to treatment arms. (A) Better efficacy subgroup (B) Poorer efficacy subgroup.

Figure 3

Figure 3

Forest plot of overall survival for the better and poorer efficacy subgroups. CI, confidence interval. Adjusted HR: Hazard ratio adjusted on baseline value of performance status, prior bevacizumab, age, hypertension and number of metastatic organs.

Figure 4

Figure 4

Progression free survival for the better efficacy subgroup by treatment arms.

Similar articles

Cited by

References

    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet] Lyon, France: International Agency for Research on Cancer; 2010.
    1. Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Köhne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, Glynne-Jones R, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol. 2012;23:2479–2516. doi: 10.1093/annonc/mds236. - DOI - PubMed
    1. Masi G, Vasile E, Loupakis F, Cupini S, Fornaro L, Baldi G, Salvatore L, Cremolini C, Stasi I, Brunetti I, Fabbri MA, Puglisi M, Trenta P, Granetto C, Chiara S, Fioretto L, Allegrini G, Crinò L, Andreuccetti M, Falcone A. Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis. J Natl Cancer Inst. 2011;103:21–30. doi: 10.1093/jnci/djq456. - DOI - PubMed
    1. Sanoff HK, Sargent DJ, Campbell ME, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Goldberg RM. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 2008;26:5721–5727. doi: 10.1200/JCO.2008.17.7147. - DOI - PMC - PubMed
    1. Hess GP, Wang PF, Quach D, Barber B, Zhao Z. Systemic Therapy for Metastatic Colorectal Cancer: Patterns of Chemotherapy and Biologic Therapy Use in US Medical Oncology Practice. J Oncol Pract. 2010;6:301–307. doi: 10.1200/JOP.2010.000072. - DOI - PMC - PubMed
Pre-publication history
    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/605/prepub

Publication types

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources