497O - Bevacizumab-erlotinib as maintenance therapy in metastatic colorectal cancer. Final results of the GERCOR DREAM study

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Benoist Chibaudel
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors B. Chibaudel1, C. Tournigand2, B. Samson3, W. Scheithauer4, P. Mesange5, G. Lledo6, F. Viret7, J.F. Ramée8, N. Tubiana-Mathieu9, J. Dauba10, O. Dupuis11, Y. Rinaldi12, M. Mabro13, N. Aucoin14, J. Latreille15, F. Bonnetain16, C. Louvet17, A.K. Larsen5, T. André18, A. De Gramont19
  • 1Clinical And Translational Research, GERCOR, 75011 - PARIS/FR
  • 2Medical Oncology, Hôpital Henri Mondor, APHP, PARIS/FR
  • 3Hémato-oncologie, Hopital Charles LeMoyne, GREENFIELD PARK/CA
  • 4Oncology, Medical University of Vienna, AT-1090 - Wien/AT
  • 5Biology, Hôpital Saint-Antoine, PARIS/FR
  • 6Gastroenterology, Hôpital privé Jean Mermoz, LYON/FR
  • 7Medical Oncology, Institut Paoli Calmettes, MARSEILLE/FR
  • 8Medical Oncology, Centre Catherine de Sienne, 44202 - Nantes/FR
  • 9Medical Oncology, CHU Limoges - Hopital Dupuytren, 87042 - Limoges/FR
  • 10Pneumologie, CH, Mont-de-Marsan/FR
  • 11Medical Oncology, Centre Jean Bernard, 72000 - Le Mans/FR
  • 12Medical Oncology, Hopital Ambroise Pare, MARSEILLE/FR
  • 13Medical Oncology, Hopital Foch, SURESNES/FR
  • 14Medical Oncology, Cité-de-la-Santé Hospital, Laval/CA
  • 15Medical Oncology, Hopital Charles LeMoyne, CA-J4V 2H1 - Greenfield Park/CA
  • 16Methodological And Quality Of Life In Oncology Unit, Ea 3181, University Hospital of Besançon, 25030 - Besançon/FR
  • 17Medical Oncology, Institut Mutualiste Montsouris, PARIS/FR
  • 18Department Of Medical Oncology, Hôpital Saint Antoine, FR-75012 - Paris/FR
  • 19Medical Oncology, Hopital St. Antoine, FR-75571 - Paris CEDEX/FR

Abstract

Aim

VEGF or EGFR targeted monoclonal antibodies with chemotherapy demonstrated clinical activity in metastatic colorectal cancer (mCRC). Yet, combining these monoclonal antibodies in mCRC achieved adverse outcomes. However, erlotinib (E), an EGFR tyrosine kinase inhibitor, combined with bevacizumab (B) as maintenance (m) therapy after B-based induction therapy (IT) improved progression-free survival (PFS) (Tournigand, ASCO 2012). We report here the final results of the DREAM study.

Methods

DREAM is a phase III trial in patients with unresectable mCRC. Pts without progression or surgery after a B-based IT were randomised to B (7.5 mg/kg q3w) or B (same dose) plus E (150 mg/d) as maintenance therapy until progression after stratification by centre, baseline ECOG status, ALP, LDH, induction chemotherapy (XELOX2-B vs mFOLFOX7-B or FOLFIRI-B), KRAS status, age, number of metastatic sites and tumour response (RR). Primary endpoint was mPFS from randomisation. Secondary endpoints were overall survival (OS), PFS from registration (r), response according to KRAS status, adverse events, curative resection, chemotherapy-free interval (CFI), and HR-QoL.

Results

Among 701 registered pts, 452 were randomised for maintenance (B, 228; BE, 224). Median follow-up was 50 months. B arm vs BE arm, medians were: mPFS 4.9 vs 5.9 months (HR 0.77, CI 0.62-0.94; p = 0.012), rPFS 9.3 vs 10.2 months (HR 0.76, 95%CI 0.63-0.93; p = 0.007), mOS 22.0 vs 25.0 months (HR 0.80, CI 0.63-0.98; p = 0.034), rOS 26.9 vs 30.5 months (HR 0.80, CI 0.64-0.99; p = 0.040). All subgroups, including KRAS, had a benefit in OS. RR from baseline maintenance were B vs BE arm: all patients 11.5% vs 22.5% (OR 0.45, CI 0.25-0.79; p = 0.003), KRAS WT 15.4% vs 24% (OR 0.58, CI 0.27-1.19; p = 0.133), KRAS mut 8.3% vs 19.7% (OR 0.37, CI 0.12-1.04; p = 0.041). Patients in the B arm vs BE arm experienced less grade 3/4 diarrhea (0.9% vs 9.3%) and skin rash (0% vs 21.4%). Median time on therapy was 110 days in arm BE.

Conclusions

Combination of erlotinib and bevacizumab as maintenance therapy significantly prolonged PFS and OS in patients with unresectable mCRC. The combination of anti-VEGF mab and EGFR tyrosine kinase inhibitor is active, even in mutated KRAS patients.

Disclosure

B. Chibaudel: Roche, Sanofi; C. Tournigand: Roche, Sanofi; F. Bonnetain: Roche, Nestlé, Merck; T. André: Roche; A. De Gramont: Roche, Sanofi. All other authors have declared no conflicts of interest.