Modified fluorouracil, oxaliplatin, and irinotecan (mFOLFOXIRI) with cetuximab does not improve progression-free rates (PFR), but may lead to improved surgical resection rates, among some patients with metastatic colorectal cancer (mCRC), according to a study published in JAMA Oncology.1
For the prospective, non-comparative phase 2 MACBETH study (ClinicalTrials.gov Identifier: NCT02295930), researchers randomly assigned 143 patients with mCRC to receive 4 months of cetuximab plus mFOLFOXIRI induction every 2 weeks, followed by cetuximab or bevacizumab maintenance therapy.
Of the 143 enrolled patients, 116 patients had RAS and BRAF wild-type mCRC, and were included in the modified intention-to-treat (mITT) population.
After a mean follow-up of 44.0 months, neither study arm reached the primary endpoint of improving the 10-month PFR over standard therapies. The 10-month PFR among patients in the cetuximab maintenance arm was 50.8% (90% CI, 39.5%-62.2%) vs 40.4% (90% CI, 29.4%-52.1%) in the bevacizumab arm.
The overall response rate was 71.6% among the 116 patients in the mITT; the disease control rate was 90.5%. Nearly 76% of patients had early tumor shrinkage.
The most frequently observed grade 3 to 4 adverse events included neutropenia, diarrhea, skin toxic effects, asthenia, stomatitis, and febrile neutropenia.
The authors concluded that although the primary endpoint was not met, “a short induction with mFOLFOXIRI plus cetuximab is feasible as first-line treatment for mCRC and allows achieving impressive activity results in RAS and BRAF wild-type patients, thus emerging as an appealing treatment option especially when a rapid and consistent tumor shrinkage is required.”
- Cremolini C, Antoniotti C, Lonardi S, et al. Activity and safety of cetuximab plus modified FOLFOXIRI followed by maintenance with cetuximab or bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer. JAMA Oncol. 2018 Feb 15. doi: 10.1001/jamaoncol.2017.5314 [Epub ahead of print]