Maintenance Treatment for Metastatic Colorectal Cancer

For patients with metastatic colorectal cancer (CRC) who achieved a response or stable disease after chemotherapy, options include a chemotherapy holiday, continuation of combination chemotherapy and a targeted agent, or institution of fluorinated pyrimidine monotherapy with a targeted agent. In maintenance studies, progression-free survival (PFS) is consistently superior with therapy continuation than with a chemotherapy holiday. Maintenance studies also indicate superior PFS for continuation of a fluorinated pyrimidine and a targeted agent over a fluorinated pyrimidine alone.

Investigators now have reported results of the industry-supported, open-label, phase 3 ERMES maintenance trial for patients with RAS/BRAF wild-type metastatic CRC who were randomized to either FOLFIRI/cetuximab until disease progression or FOLFIRI/cetuximab for 4 months followed by maintenance with cetuximab alone. Of 593 patients treated, 337 patients with response or stable disease at 4 months (57%) proceeded to therapy continuation or maintenance cetuximab. Most patients had undergone surgery (61%), had one metastatic disease site (80%), and had left-sided (71%) versus right-sided (19%) primary tumors.

The primary endpoint of noninferior PFS was not met for cetuximab compared with FOLFIRI/cetuximab (median, 10.0 vs. 12.2 months; hazard ratio, 1.3), exceeding the study's noninferiority boundary. Grades 3 and 4 adverse events during the maintenance phase were numerically more common with FOLFIRI/cetuximab (35.1%) than with cetuximab (20.2%). Rates of overall response were similar for the two arms (67.5% and 71.6%, respectively). Cetuximab maintenance showed a nonsignificant trend toward superiority in overall survival (35.7 months; FOLFIRI/cetuximab, 30.7 months; HR, 0.79; P=0.119).