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

• 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

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

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

Treatment scheme

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%

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

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

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

Pre-study and on-study treatment regimens

Patient baseline characteristics

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%)

Relevant grade 3 / 4 adverse events

Overall survival

n=1147*

Overall survival by irinotecan regimen

Progression-free survival

n=1147*

Progression-free survival by irinotecan regimen

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

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

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