Cetuximab maintenance therapy in unresectable metastatic colorectal cancer patients with wild-type RAS and BRAF: A single-center retrospective study.

Abstract

e15004 Background: Cetuximab plus FOLFIRI (leucovorin, fluorouracil and irinotecan) is preferred first line therapy for RAS and BRAF wild-type (RBWT) metastatic colorectal cancer (mCRC) patients. However, the side effects often require dose-reductions or discontinuation calling for maintenance strategies to reduce toxicity and preserve efficacy. Therefore, we evaluated efficacy and safety of cetuximab maintenance therapy after first-line treatment in unresectable mCRC patients with RBWT. Methods: This single center, retrospective study enrolled patients (aged 18-71 years) with untreated mCRC with RBWT, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, with at least one measurable lesion according to response evaluation criteria in solid tumor (RECIST). All patients received first line cetuximab plus FOLFIRI every two weeks for 9-12 cycles, after which, patients with treatment response chose to either enter observation (stop treatment) or maintenance 1 (cetuximab plus irinotecan) group. After 6-12 cycles of maintenance 1, patients with treatment response entered maintenance 2 (cetuximab only). If patients progressed on maintenance 2, reintroduction of cetuximab plus FOLFIRI was suggested. Primary endpoint was failure-free survival (FFS); while secondary endpoints included disease control rate (DCR), objective remission rate (ORR) and progression free survival (PFS). Safety events were also evaluated. Results: Among 62 enrolled patients, 56 patients completed first-line treatment (DCR: 90.3%, ORR: 62.9%) and 30 patients entered maintenance 1 [median PFS1 (mPFS) =6.1 months, 95%CI: 6.0-6.2, DCR=60%, ORR=30%]. Of these, 18 entered maintenance 2 [mPFS2=6.6 months, 95%CI: 5.1-8.1, DCR=27.8%, ORR=5.6%]. The mFFS was significantly longer in maintenance 1 (12.8 months, 95%CI: 10.8-14.8) compared to observation group (3.0 months; hazard ratio [HR]: 0.21, 95%CI: 2.6-3.4, P<0.001). Overall mFFS was 19.0 (95%CI: 11.0-27.0) in maintenance and 9.5 months in observation group (HR: 0.195, 95%CI: 7.4-11.6; P<0.001). Rash acneiform, mucositis and asthenia were the common adverse events observed during maintenance treatment. Conclusions: Maintenance treatment with cetuximab after first line therapy significantly improved FFS, with acceptable safety profile in untreated mCRC RBWT patients.