MACRO-2 Trial: Maintenance Therapy with Single-Agent Cetuximab plus Chemotherapy after Cetuximab-Based Induction for Patients with Metastatic Colorectal Cancer
The treatment options in patients with metastatic colorectal cancer (mCRC) include chemotherapy and targeted agents. Single-agent bevacizumab has been evaluated as maintenance therapy after induction therapy with bevacizumab plus chemotherapy; however, the role of cetuximab in this setting has not been evaluated. At ESMO 2014, Alfonso and colleagues from the Spanish Cooperative Group presented the results of the randomized, multicenter, phase 2 MACRO-2 clinical trial that assessed the efficacy and safety of maintenance cetuximab as a single agent or with a modified FOLFOX-6 (mFOLFOX-6) regimen after induction with mFOLFOX-6 plus cetuximab therapy in treatment-naïve patients with mCRC (Alfonso et al. The MACRO-2 trial. ESMO 2014: Abstract 4990).
The MACRO-2 trial included 193 patients with wild-type KRAS exon 2 who received first-line therapy of cetuximab 250 mg/m2 weekly plus mFOLFOX-6 every 2 weeks for 8 cycles. The patients were then randomized into 1 of 2 treatments to receive maintenance therapy with either single-agent cetuximab (n = 129) or cetuximab plus mFOLFOX-6 (n = 64), until disease progression. The primary end point was progression-free survival (PFS); secondary end points were overall survival, objective response rate, and safety.
At a median follow-up of 13.9 months, the rate of PFS at 9 months was similar between the single-agent cetuximab and cetuximab-chemotherapy arms (63.6% vs 71.9%, respectively; odds ratio, 0.6827; P = .25), with a median PFS of 23.6 months and 22.2 months, respectively. The safety analysis showed no differences in the overall incidence of grade 3 or 4 toxicities between the 2 treatment arms (61.4% vs 59.7%, respectively); however, as expected, neuropathy was more common in the oxaliplatin-containing arm. Grade 3/4 toxicities reported were neutropenia (25.2% vs 26%), rash acneiform (13% vs 22.6%), neuropathy (2% vs 15%), asthenia (8% vs 5%), diarrhea (7% vs 6%), and mucositis (7% vs 6%).
Based on these results, the investigators concluded that single-agent cetuximab was noninferior to mFOLFOX-6 plus cetuximab when used as maintenance therapy after induction therapy with cetuximab plus mFOLFOX-6, and it may be a reasonable treatment option for patients with mCRC..