559P - Efficacy and safety of treatment with bevacizumab (BEV) + chemotherapy (CT) beyond first progression in patients (pts) with metastatic colorectal ca...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Olivier Bouché
Authors O. Bouché1, C. Steffens2, T. André3, J. Bennouna4, J. Sastre5, P.J. Osterlund6, R. von Moos7, I. Reyes-Rivera8, M.A. Sersch9, D. Arnold10
  • 1Centre Hospitalier Universitaire Robert Debré, Reims/FR
  • 2MVZ Haematologie/Onkologie Klinik Dr. Hancken, Stade/DE
  • 3Medical Oncology, Hopital Saint-Antoine and Université Pierre et Marie Curie, Paris/FR
  • 4Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes/FR
  • 5Medical Oncology, Servicio de Oncología Médica HC, Madrid/ES
  • 6Medical Oncology, Helsinki University Central Hospital, Helsinki/FI
  • 7Medical Oncology, Kantonal Hospital Graubünden, Chur/CH
  • 8Statistics, Genentech Inc., South San Francisco/US
  • 9Global Development, Genentech Inc., South San Francisco/US
  • 10Medical Oncology, Hubertus Wald Tumor Center, University Cancer Center Hamburg (UCCH), Hamburg/DE

Abstract

Background

The ML18147 study showed that BEV + standard CT as second-line treatment for pts with mCRC who progressed after first-line BEV-containing CT significantly improved survival with an acceptable toxicity profile. However, more evidence is needed that current treatment options are tolerable and efficacious in older pts. Here, we assessed efficacy and safety according to age in the ML18147 study.

Methods

Pts with unresectable, histologically confirmed mCRC who progressed <3 months from discontinuing first-line BEV were randomised to second-line fluoropyrimidine-based CT ± BEV (2.5 mg/kg/wk equivalent). Choice of second-line oxaliplatin or irinotecan depended on first-line regimen (crossover). We present a post-hoc analysis of overall survival (OS), progression-free survival (PFS) and tolerability in pts <65 years vs ≥65 years of age.

Results

820 pts were randomised, 409 to BEV + CT and 411 to CT alone. 458 pts were <65 years and 361 pts were ≥65 years of age. PFS was statistically significantly longer with BEV + CT vs CT alone in pts <65 years (median 5.9 vs 3.9 months; HR = 0.66; 95% CI 0.55–0.80; p < 0.0001) and ≥65 years (5.5 vs 4.3 months; HR = 0.71; 95% CI 0.57–0.87; p = 0.0011). OS was statistically significantly longer with BEV + CT in pts <65 years (median 11.6 vs 9.9 months; HR = 0.79; 95% CI 0.65–0.98; p = 0.0274) and numerically but not significantly longer in pts ≥65 years (10.7 vs 9.8 months; HR = 0.83; 95% CI 0.66–1.04; p = 0.1056). The incidence of grade 3–5 AEs in pts receiving BEV + CT or CT alone in both age groups is shown in the Table.

< 65 years ≥ 65 years
CT alone BEV + CT CT alone BEV + CT
% of Patients (n = 230) (n = 222) (n = 179) (n = 179)
Grade 3–5 AEs 54 64 62 63
Grade 3–5 AEs of special interest for BEV
Hypertension <1 2 2 1
Proteinuria 0 <1 0 <1
Bleeding/haemorrhage <1 2 0 2
Abscess/fistula 0 <1 0 1
GI perforation <1 2 <1 2
Congestive heart failure <1 0 <1 0
Venous thromboembolic event 3 5 3 5
Arterial thromboembolic event 0 <1 1 <1
Wound-healing complications 0 <1 <1 0
Deaths not due to progression 4.3 5.0 6.7 6.7

Conclusions

This subgroup analysis of ML18147 suggests that the addition of BEV to CT after disease progression improves PFS and OS in pts <65 years and ≥65 years of age. The incidence of grade 3–5 AEs was similar within age groups.

Disclosure

O. Bouche: Consultant / advisory board: Roche Honoraria: Roche.

C. Steffens: Advisory Board: Roche Honoraria: Roche.

T. André: Consultant / advisory board: Roche.

J. Bennouna: Consultant / advisory board: Roche, Honoraria: Roche.

J. Sastre: Honoraria: Roche Research funding: Roche.

P. Österlund: Consultant / advisory board: Roche Honoraria: Roche.

R. von Moos: Consultant/advisory board: Roche, Honoraria: Roche, Research funding: Roche.

I. Reyes-Rivera: Employed by Genentech Inc.

M.A. Sersch: Employed by Genentech Inc.

D. Arnold: Consultant / Advisory Board: Roche, Honoraria: Roche, Research funding: Roche.