As reported in the Journal of Clinical Oncology by Pinto et al, the Italian phase III ERMES trial showed that the addition of cetuximab maintenance to eight cycles of first-line FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus cetuximab did not achieve noninferiority in terms of progression-free survival vs FOLFIRI/cetuximab given until disease progression in patients with RAS/BRAF wild-type metastatic colorectal cancer.
Study Details
In the open-label multicenter trial, 606 patients were randomly assigned to receive FOLFIRI plus cetuximab at a 400 mg/m2 loading dose on week 1 and then 250 mg/m2 weekly until disease progression (n = 300) or FOLFIRI/cetuximab for eight cycles followed by cetuximab alone (n = 306).
The primary endpoints were:
- Noninferior progression-free survival in the cetuximab-alone maintenance group in the modified-per-protocol (mPP) population (ie, those who received > 8 cycles of treatment), including 154 patients in the FOLFIRI/cetuximab group and 183 in the cetuximab-alone maintenance group
- A lower incidence of grade 3 or 4 adverse events in the cetuximab-alone maintenance group in the intention-to-treat (ITT) population (receipt of > 1 cycle).
Key Findings
Median follow-up was 22.3 months. In the mPP population, median progression-free survival was 10.0 months in the cetuximab-alone maintenance group vs 12.2 months in the FOLFIRI/cetuximab group (P for noninferiority = .43). In the ITT population, median progression-free survival was 9.0 months vs 10.7 months (P = .39). Median overall survival was 35.7 months vs 30.7 months (P = .119) in the mPP population and 31.0 months vs 25.2 months (P = .32) in the ITT population.
Formal analysis of incidence of grade 3 or 4 adverse events was not performed due to absence of significance in the progression-free survival analysis. Overall, grade 3 or 4 adverse events occurred in 50.3% vs 52.0 % of patients, including 20.2% vs 35.1% in the maintenance phase.
The investigators concluded, “The ERMES study did not demonstrate noninferiority of maintenance with cetuximab alone. Despite a more favorable safety profile, maintenance with single-agent cetuximab after induction with FOLFIRI/cetuximab cannot be recommended for all patients but could represent an option in selected cases.”
Armando Orlandi, MD, PhD, of UOC di Oncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCC, Rome, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Serono S.p.A., Italy, and an affiliate of Merck KGaA, Darmstadt. For full disclosures of the study authors, visit ascopubs.org.
