Cetuximab Combinations Promising in Phase II Trials

November 1, 2006

Adding the targeted antibody cetuximab (Erbitux) to standard cytotoxic chemotherapy as first-line treatment for patients with advanced colorectal cancer improves response rates, two groups of researchers said at the 31st Congress of the European Society for Medical Oncology (ESMO).

ISTANBUL, Turkey--Adding thetargeted antibody cetuximab (Erbitux)to standard cytotoxic chemotherapy asfirst-line treatment for patients with advancedcolorectal cancer improves responserates, two groups of researcherssaid at the 31st Congress of the EuropeanSociety for Medical Oncology (ESMO).

At an ESMO press briefing, VolkerHeinemann, MD, PhD, of KlinkumGrosshadern, Munich, Germany, describeda phase II study (abstract 327 O)in which patients were randomly assignedto XELIRI-capecitabine (Xeloda) 800mg/m2 twice daily orally on days 1 to 14and irinotecan (Camptosar) 200 mg/m2intravenously on day 1-or XELOX-capecitabine 1,000 mg/m2 twice daily ondays 1 to 14 and oxaliplatin (Eloxatin)130 mg/m2 intravenously on day 1. Inboth arms, cetuximab was given at a doseof 400 mg/m2 intravenously on day 1 ofthe first 3-week cycle and then at 250mg/m2 for each subsequent cycle.

The overall response rate (completeand partial responses) in the XELIRI/cetuximab arm was 42.4% (14 of 33 patients)and in the XELOX arm, 65.5%(19 of 29 patients). Disease control (respondersplus patients with stable disease)was 91% for XELIRI/cetuximab and93% for XELOX/cetuximab.

The most common grade 3–4 toxicitiesin both arms were skin toxicity, allergicreactions, diarrhea, neurotoxicity, andleukopenia. There were more hematologicaladverse events in the irinotecanarm and more nonhematological adverseevents in the oxaliplatin arm.

"In summary," Dr. Heinemann said,"cetuximab enhances the activity of cytotoxicchemotherapy. New agents likethe monoclonal antibodies cetuximab orbevacizumab [Avastin] hold promise toprolong survival among patients withmetastatic colorectal cancer."

Cetuximab Plus XELOX
Another study (abstract 328 O) comparedXELOX with or without cetuximab.The study was conducted by DanielHelbling, MD, of University HospitalBern, and his colleagues through the SwissGroup for Clinical Cancer Research(SAKK). Compared with other colon cancerchemotherapy regimens, XELOX iseasy to administer, Dr. Helbling said. Patientsattend the clinic once every 3 weeksfor an infusion of oxaliplatin and takecapecitabine tablets for 14 days.

In the multicenter, randomized phaseII trial, patients were given oxaliplatin130 mg/m2 on day 1 and oral capecitabine1,000 mg/m2 twice daily on days 1 to 14every 21 days, with or withoutcetuximab 250 mg/m2 weekly followinga loading dose of 400mg/m2. Therapy was stoppedafter a maximum of six cycles.

The preliminary results showed improvements in responserates for the combinationarm. Patients in the cetuximab/XELOX group had a response rate of 43% vs 27% for the XELOX alonegroup at 9 weeks, and 43%vs 22% at 18 weeks. The stabledisease rates were 46% vs 32%at 9 weeks and 22% vs 11% at18 weeks. "The combinationof XELOX and cetuximab waseasy to take and caused few sideeffects," Dr. Helbling said. "Wewere amazed that it was so well tolerated."The trial produced significant toxicitiesin less than 10% of cycles in eacharm. Skin rash of grade 3-4 occurred in6% of cycles in the cetuximab arm.

Overall, the results were very positive,Dr. Helbling said, although he stressedthat these are preliminary results. "Thestudy shows that the combination ofXELOX and cetuximab would be a goodcandidate for first-line therapy."