A randomized study evaluating the continuation of bevacizumab  beyond progression in metastatic colo...
This presentation is the property of its rightful owner.
Sponsored Links
1 / 22

Disclosure: Gianluca Masi PowerPoint PPT Presentation


  • 78 Views
  • Uploaded on
  • Presentation posted in: General

A randomized study evaluating the continuation of bevacizumab beyond progression in metastatic colorectal cancer patients who received bevacizumab as part of first-line treatment: results of the BEBYP trial by the Gruppo Oncologico Nord Ovest (GONO).

Download Presentation

Disclosure: Gianluca Masi

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Disclosure gianluca masi

A randomized study evaluating the continuation of bevacizumab beyond progression in metastatic colorectal cancer patients who received bevacizumab as part of first-line treatment: results of the BEBYP trial by the GruppoOncologico Nord Ovest (GONO).

G. Masi1, F. Loupakis1, L. Salvatore1, L. Fornaro1, C. Cremolini1, M. Schirripa1, E. Fea2,C. Granetto2, L. Antonuzzo3, E. Giommoni3, G. Allegrini4, S. Cupini5, C. Boni6, M. Banzi6, S. Chiara7, C. Sonaglio7, C. Valsuani8, A. Bonetti9, L. Boni10, A. Falcone1,11

1) Pisa, Italy; 2) Cuneo, Italy; 3) Firenze, Italy; 4) Pontedera, Italy; 5) Livorno, Italy 6) Reggio Emilia, Italy; 7) Genova, Italy; 8) Lido di Camaiore, Italy; 9) Legnago, Italy; 10) Istituto Toscano Tumori, Firenze, Italy; 11) Università di Pisa, Italy.


Disclosure gianluca masi

Disclosure: GianlucaMasi

  • Honoraria: Roche, Merck-Serono, Amgen

  • ResearchFunding: Roche


Disclosure gianluca masi

Background

  • BV plus fluoropyrimidine-based CT is a standard first-line treatment in mCRC pts.

  • Retrospective data from BRITE and ARIES studies suggested that the continuation of BV with second line CT beyond progression was associated with improved survival 1,2.

  • A recent phase III study (AIO/AMG ML18147) demonstrated an improved survival with BV beyond progression 3.

  • Grothey et al. JCO 2008;26:5326-34

  • Cohn et al. JCO 2010;28(15s):Abstr 3596

  • Arnold et al. JCO 2012;30 (suppl; abstr CRA3503)


Disclosure gianluca masi

Study Design

R

A

N

D

O

M

A. Second-line CT§

  • I-line CT * + BV

  • Stratification

  • Center

  • PS 0/1-2

  • CT-free interval

  • (> vs ≤ 3 mos)

  • II-line CT

B. Second-line CT§+ BV

*

  • FOLFIRI

  • FOLFOX

  • FOLFOXIRI

  • Fluoropyrimidine mono-tx

  • FOLFIRI

  • mFOLFOX-6

§

  • Study conducted in 19 Italian centers

  • Supported by AIFA


Disclosure gianluca masi

Treatment schedules

  • FOLFIRI

  • IRINOTECAN 180 mg/sqmi.v. over 1 hr on day 1 concomitantly with

  • l-LV 200 mg/sqmi.v. over 2 hrs on days 1 followed by

  • 5-FU 400 mg/sqmi.v. bolus on days 1 followed by

  • 5-FU 2400 mg/sqmi.v. by c.i. over 46 hrs on days 1

  • cycles repeated every 2 weeks

  • mFOLFOX-6

  • OXALIPLATIN 85 mg/sqmi.v. over 1 hr on day 1 concomitantly with

  • l-LV 200 mg/sqmi.v. over 2 hrs on days 1 followed by

  • 5-FU 400 mg/sqmi.v. bolus on days 1 followed by

  • 5-FU 2400 mg/sqmi.v. by c.i. over 46 hrs on days 1

  • cycles repeated every 2 weeks

  • In pts randomized to the BV containing arm the regimens were associated with:

  • BEVACIZUMAB5 mg/kgi.v. on day 1 (immediately before irinotecan or oxaliplatin) repeated every 2 weeks


Disclosure gianluca masi

Objectives

  • Primary

  • Progression Free Survival

  • Secondary

  • Response Rate

  • Overall Survival

  • Safety

  • Potential markers predictive of BV activity


Disclosure gianluca masi

Statistical Design / Accrual

  • Original Hypothesis

    • To detect a HR for PFS of 0.70 in favor of CT+BV

    • Power=80%; alpha, two-sided=0.05

    • Required 249 events and a total of 262 pts

  • Accrual started on April 8th 2008 and was stopped prematurely on May 11th 2012

    • Press release of TML study results with OS improvement

    • Slow accrual rhythm due to bevacizumab supply limitation

  • Randomized 185 pts (184 pts for ITT) (1 pt randomized twice)


Disclosure gianluca masi

Main Eligibility Criteria

  • Pts with histologicallyconfirmedcolorectaladenoca

  • Age >18 yrs and <75 yrs

  • ECOG PS 0-2

  • Unresectable and measurable metastatic disease according to RECIST criteria

  • Progressive disease after or during first-line CT with fluoropyrimidine, FOLFIRI, FOLFOX + BV or >3 mos after the last dose of FOLFOXIRI + BV


Disclosure gianluca masi

Patients’ characteristics (1)

* By central analysis


Disclosure gianluca masi

Patients’ characteristics (2)


Disclosure gianluca masi

Second-line CT on the basis of first-line CT


Disclosure gianluca masi

Primary Objective - PFS

CT (85 events) median PFS = 4.97 mos

CT+ B (87 events) median PFS = 6.77 mos

HR=0.65 (95%CI 0.48-0.89)

p=0.0062

Median follow up 18.0 mos


Disclosure gianluca masi

Subgroup Analysis of PFS

*

* Test of interaction


Disclosure gianluca masi

Response Rate

* p not statistically significant (0,71)

** p not statistically significant (0,21)


Disclosure gianluca masi

OverallSafety

* CNS ischemia


Disclosure gianluca masi

Maximum Toxicities per patient(CT related)


Disclosure gianluca masi

Maximum Toxicities per patient(Beva-related)


Disclosure gianluca masi

Subsequent anti-cancer therapies


Disclosure gianluca masi

Overall Survival

  • OS data are still immature

  • After a median follow up of 18 months we observed 52 events in arm A (CT) and 46 events in arm B (CT+BV)


Disclosure gianluca masi

Summary

  • Bevacizumab beyond progression significantly improved PFS

    • CT vs CT+BV: mPFS 4.97 vs 6.77 months

    • HR=0.65 (95% CI 0.48-0.89), p=0.0062

  • Data from subgroup analyses for PFS consistent with overall population

  • No significant differences in RR and DCR

  • OS data still immature

  • Safety profile consistent with previously reported data


  • Disclosure gianluca masi

    Conclusions

    • Second randomized trial investigating the impact of BV continuation beyond first progression

    • Our results are in line with those of TML

    • The prosecution of BV in combination with second-line CT represents a new treatment option


    Disclosure gianluca masi

    Acknowledgements

    • Patients and their caregivers

    • AIFA

    • Dr. Luca BoniCentro CoordinamentoSperimentazioniCliniche, IstitutoToscanoTumori

    • Investigators

    • Pisa (A. Falcone, G. Masi, F. Loupakis, L. Salvatore, C. Cremolini, M. Schirripa, L. Fornaro)

    • Cuneo (M. Merlano, C. Granetto, E. Fea)

    • Livorno (F. Cappuzzo, S. Cupini, C. Barbara)

    • Firenze (F. Di Costanzo, L. Antonuzzo, E. Giommoni)

    • Reggio Emilia (C. Boni, M. Banzi, R. Gnoni)

    • Genova IST (P. Pronzato, S. Chiara, C. Sonaglio)

    • Versilia (D. Amoroso, C. Valsuani)

    • Pontedera (G. Allegrini, L. Marcucci, S. Lucchesi)

    • Legnago (A. Bonetti, F. Greco)

    • Piombino (F. Dargenio, V. Safina)

    • Biella (M. Clerico)

    • Lecce (V. Lorusso, A. Gambino)

    • Novara (O. Alabiso)

    • Siena (S. Crispino, S. Biancanelli, A. Martignetti)

    • Fabriano (RR Silva, E. Galizia)

    • Pesaro (V. Catalano)

    • Caltanissetta (S. Vitello)

    • Empoli (G. Fiorentini)

    • Parma (A. Ardizzoni)


  • Login