A phase II study of the anti-IGFR antibody MK-0646 in combination with cetuximab and irinotecan in the treatment of chemorefractory metastatic colorectal cancer

Abstract

4127 Background: Evidence of cross-talk between EGFR and IGFR signaling pathways provide a logical rationale for combining anti-EGFR and anti-IGFR strategies in the treatment of cancer. Prior to commencing a blinded randomised phase II study, an opened-labelled safety run-in was undertaken to assess the tolerability of a three-drug combination utilizing irinotecan (Ir), cetuximab (Cx) and two schedules of MK-0646 (Mk). Methods: Eligible patients (pts) had previously failed both Ir and oxaliplatin and had progressed on or within 3 months of their last therapy. Pts were required to have measurable disease and tissue samples available for tumour KRAS testing. Pts were randomised to receive either Mk 10mg/kg weekly (Arm A) or Mk 15mg/kg loading followed by 7.5mg/kg every alternate week (Arm B). All randomised pts also received Cx 400mg/m2 loading followed by 250mg/m2 weekly and Ir according to the same dose and schedule as they had previously received. Patients continued on treatment until disease progression with radiological response assessments undertaken every 6 weeks. Results: 10 pts were recruited to Arm A and 8 to Arm B. Pt characteristics: median age 60.5 years, male 67%, PS 0/1 33%/67%. Median number of prior chemotherapy regimens 3. The median number of cycles of Mk received in Arm A and B is 25 and 8 respectively. Reported grade III/IV toxicities in Arm A and Arm B were: neutropenia 30% and 0%, diarrhoea 30% and 25%, hypomagnesemia 0% and 25%. Hyperglycemia (≥ grade 2) was seen in 10% of Arm A and 25% in Arm B. Acneiform skin toxicity (≥ grade 2) was seen in 30% of Arm A and 62% of Arm B. The radiological response rate was 33% in Arm A and 14% in Arm B. The median time on study drug is 5.8 months in Arm A and 3.9 months in Arm B. 2 pts on Arm A and 1 in Arm B remain on study therapy. Tumour KRAS testing is in progress. Conclusions: The combination of MK-0646, cetuximab and irinotecan is tolerable with no concerning overlapping toxicities highlighted. PFS and KRAS data will be available for presentation. The efficacy of this three drug combination is under evaluation in an ongoing randomised phase II/III study. [Table: see text]