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Background

MABEL – a large multinational study of cetuximab plus irinotecan in metastatic colorectal cancer progressing on irinotecan H Wilke, R Glynne-Jones, J Thaler, A Adenis, P Preusser, E Aranda Aguilar, MS Aapro, N van den Berg, SP Eggleton, S Siena. Background.

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Background

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  1. MABEL – a large multinational study of cetuximab plus irinotecan in metastatic colorectal cancer progressing on irinotecanH Wilke, R Glynne-Jones, J Thaler, A Adenis, P Preusser, E Aranda Aguilar, MS Aapro, N van den Berg, SP Eggleton, S Siena

  2. Background • Globally, CRC is the fourth most common cancer in men and the third in women • The 5-year survival for patients with metastatic CRC is 5-30% • The epidermal growth factor receptor (EGFR) is expressed in 75-89% of CRCs and is associated with decreased survival • Cetuximab is an IgG1 monoclonal antibody targeting the EGFR • The BOND study demonstrated the efficacy of cetuximab in mCRC progressing on irinotecan

  3. MABEL study • MABEL is a multicenter, open, uncontrolled study investigating cetuximab + irinotecan in patients with EGFR-detectable mCRC whose last treatment regimen contained irinotecan • Patients from 8 European countries • MABEL is to date the largest cetuximab study published in this setting • This presentation reports pre-final data of the MABEL study

  4. Study objectives • Primary objectives • To determine the PFS rate at 12 weeks after initiation of cetuximab treatment • Secondary objectives: • To determine PFS at 24 weeks after initiation of cetuximab treatment and every 12 weeks thereafter • To determine the median overall survival time and the survival rate at 6 months after the initiation of cetuximab treatment and every 6 months thereafter • Safety and toxicity

  5. Treatment scheme

  6. Patients and methodsMain inclusion criteria • Histologically confirmed metastatic CRC • ≥ 1 bidimensionally measurable lesion • IHC evidence of EGFR expression in the primary tumor or a metastasis • Previous treatment with one of 4 pre-defined irinotecan regimens as the most recent chemotherapy treatment • Imaging-based progressive disease (PD) • Karnofsky PS ≥ 80%

  7. Patients and methodsMain exclusion criteria • Documented or symptomatic brain metastases • Radiotherapy or major surgery within 4 weeks prior to study entry • Previous exposure to EGFR-targeted therapy

  8. Assessments • Imaging of chest, pelvis and abdomen was performed at baseline and every 12 weeks during treatment • Assessment of PD was based on WHO criteria • Any death without previous progression occurring within 120 days after last tumor assessment and symptomatic deterioration leading to discontinuation of study treatment (unless CT- or MRI-scan confirmed absence of PD) was regarded as progression • Best response was based on investigator subjective assessment

  9. Results – Treatment patterns • 1147 patients were included in the intent-to-treat evaluation of safety and efficacy • 93 received irinotecan 125 mg/m2/w • 670 received irinotecan 180 mg/m2 q2w • 356 received irinotecan 350 mg/m2 q3w • 28 received irinotecan regimens other than those specified in the protocol • The median time between the end of the last cycle of pre-study irinotecan treatment and progression was 10 days

  10. Pre-study and on-study treatment regimens

  11. Patient baseline characteristics

  12. Safety • Treatment was generally well tolerated • Diarrhea and rash were the most common side effects • Grade 3 / 4 diarrhea (20%) • Grade 3 / 4 skin and subcutaneous tissue disorders (including acne-like rash) (19%)

  13. Relevant grade 3 / 4 adverse events

  14. Overall survival n=1147*

  15. Overall survival by irinotecan regimen

  16. Progression-free survival n=1147*

  17. Progression-free survival by irinotecan regimen

  18. Best response • Best response (clinical global impression) • 3 complete responses • 228 partial responses • 287 stable disease • Response rate: 20% (95% CI 18-23%) • Disease control rate: 45% (42-48%) • Best response was considered not to be evaluable in 9% of patients

  19. Conclusions (I) • The PFS rates for cetuximab + irinotecan exceeded the expected rate of 50% ± 3% • For all irinotecan regimens, similar PFS and overall survival times were seen at all time points analyzed • Treatment was well tolerated • The most common side effects were skin and subcutaneous tissue disorders • Known side effects of irinotecan were not increased compared with historical controls • The estimated median overall survival of 9.2 months is in line with that reported for cetuximab + irinotecan in the BOND study

  20. Conclusions (II) • The results of this large study (n=1147) indicate that the benefits of combining cetuximab with irinotecan noted previously in clinical studies are achievable in routine clinical practice in a wider community setting

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