Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 3549
© 2006 American Society of Clinical Oncology

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Abstract

MABEL—A large multinational study of cetuximab plus irinotecan in irinotecan resistant metastatic colorectal cancer

Kliniken Essen Mitte, Essen, Germany; Mount Vernon Hospital, London, United Kingdom; Krankenhaus der barmherzigen Schwestern Wels, Wels, Austria; Centre Oscar Lambret, Lille, France; Muenster University Clinic, Muenster, Germany; Hospital Universitario Reina Sofia, Cordoba, Spain; Institut Multidisciplinaire d’Oncologie IMO, Genolier, Switzerland; Merck KGaA, Darmstadt, Germany; Ospedale Niguarda Ca’Granada, Milano, Italy

3549

Background: Cetuximab is an IgG1 anti-EGFR monoclonal antibody, active alone and in combination with irinotecan in metastatic colorectal cancer (mCRC) patients (pts) who failed irinotecan (Cunningham et al, NEJM 2004). MABEL investigated cetuximab plus irinotecan in an uncontrolled, multicenter study in pts with EGFR-detectable mCRC whose last treatment regimen contained irinotecan. MABEL is to date the largest cetuximab study published in this setting. Methods: Primary endpoint was the progression-free survival (PFS) rate at 12 weeks (wks), (expected rate 50% ± 3%). Study treatment was cetuximab, initial dose 400 mg/m², weekly 250 mg/m², plus irinotecan with dose and schedule as pre-study: Regimen A: 125 mg/m² weekly for 4/6 wks, B: 180 mg/m² q 2 wks, or C: 350 mg/m² q 3 wks. Results: 197 centers from 7 countries screened tumors of 1681 pts for EGFR expression: 1461 (87%) pts had EGFR-detectable tumors. 1123 pts are currently evaluable: median age is 62 years (25–84), Karnofsky status 70% in all pts, and 64% pts were male. 64% pts had 2 prior therapy lines. 76% pts were also pretreated with oxaliplatin. On-study distribution of pts to irinotecan regimens was A: 92, B: 674, C: 357. 12-week PFS rates were: A: 60% (50–71%); B: 60% (56–64%); C: 63% (58–68%); overall: 61% (58–64%), and at 24 wks: A: 29% (19–39%); B: 32% (28–36%); C: 39% (34–45%); overall 34% (31–37%). The current estimate of median survival, based on 717 deaths, is 9.2 (8.7–9.9) months. Treatment was generally well tolerated with grade 3/4 adverse events >5%: diarrhea 20%, skin and subcutaneous tissue disorders incl. acne-like rash 19%, neutropenia 9%, asthenia 8%. Grade 3/4 immune system disorders incl. hypersensitivity reactions occurred in 1.5%, hypomagnesemia in 0.4% pts. Conclusions: The PFS rates observed in this heavily pretreated population fully met the primary endpoint of this study. Similar PFS rates were seen at 12 weeks (overall 61%) and 24 weeks (overall 34%) for all irinotecan regimens. Estimated survival time is in line with previously published results. MABEL clearly confirmed in a wider setting the efficacy and safety of cetuximab plus irinotecan seen in previous studies.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck, Roche, sanofi-aventis Merck, Roche, sanofi-aventis Merck, Roche

Abstract presentation from the 2006 ASCO Annual Meeting