Randomized trial comparing cetuximab plus XELIRI versus cetuximab plus XELOX as first line treatment of patients with metastatic colorectal cancer (mCRC): A study of the german AIO CRC study group

Abstract

4033 Background: Cetuximab combined with 5-fluorouracil/folinic acid (5-FU/FA) plus irinotecan or oxaliplatin has shown activity in the treatment of mCRC. This randomized trial compared the first-line efficacy of XELIRI plus cetuximab (XELIRI-C) to XELOX plus cetuximab (XELOX-C). Methods: Eligibility criteria: pts with untreated mCRC, Karnofsky performance status (KPS) >=70%, measurable lesions. Treatment plan: cetuximab 400 mg/m² was given iv on day 1 of cycle 1 and 250 mg/m² iv subsequently. In the XELIRI-C arm, pts received capecitabine (2 x 800 mg/m² po on days 1–14), and irinotecan (200 mg/m² iv on day 1) q3w. In pts >65 years doses of irinotecan and capecitabine were reduced by 20%. In the XELOX-C arm, capecitabine (2 x 1,000 mg/m2 po on days 1–14) was combined with oxaliplatin (130 mg/m² iv on day 1) q3w. The primary endpoint was the objective response rate (ORR) according to RECIST. Results: 185 pts were randomized to XELIRI-C (n=93) or XELOX-C (n=92). Median age (63 yrs vs 62 yrs), median KPS (90% vs 90%), and liver metastases (81% vs 88%) were well balanced. Pts received a median of 6 treatment cycles in both arms. In 142 evaluable pts (XELIRI-C vs XELOX-C: 74 vs 68) the ORR was 52.7% vs 61.8% and the disease control rate (CR+PR+SD) was 83.4% vs 97.1%, respectively. Median remission duration was 7.7 months vs 8.2 months, and median progression-free survival was 8.4 months (95% CI, 6.9–10.7 months) vs 9.2 months (95% CI, 8.1–11.2 months), respectively. Median overall survival has not yet been reached. The most common grade 3/4 CTC- toxicities observed in the XELIRI-C and the XELOX-C arm, respectively, were diarrhea (16.3% vs 20%), nausea (7.0% vs 9.4%), skin rash (12.8% vs 18.8%), hand-foot-syndrome (1.2% vs 2.4%), and sensory neuropathy (1.2% vs 12.9%). Conclusion: This randomized trial indicates efficacy and tolerability for cetuximab combined with XELIRI or XELOX as first-line treatment of mCRC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Germany Lilly Germany Lilly Germany