Combination Therapy Effective Against Refractive Colorectal Cancer
(Chemotherapy Advisor) — Combining cetuximab and erlotinib may be effective against certain types of chemotherapy refractive, metastatic colorectal cancer, according to a recent study published in the Journal of Clinical Oncology by Weickhardt et al. The antibody-based chemotherapeutic agents were used in a preclinical study and a Phase II clinical study to evaluate their efficacy and safety in the treatment of patients with metastatic colorectal cancer.
Preclinically, the activity and mechanism of action of the combination therapy were investigated in vitro in colorectal cell lines. In the clinical study, 50 patients with chemotherapy-refractory mCRC enrolled were first treated with cetuximab 400 mg/m2 as a loading dose. This was followed by a weekly dose of cetuximab 250 mg/m2 plus a daily oral administration of 100 mg of erlotinib. The primary end point was response rate (RR), which was evaluated separately in KRAS wild-type (WT) versus KRAS mutant tumors. Secondary end points included toxicity, progression-free survival (PFS), and overall survival.
The preclinical study demonstrated that combining cetuximab and erlotinib synergistically inhibits colon cancer cell lines, both as a result of enhanced inhibition of the epidermal growth factor receptor pathway and differential effects on STAT3. In the clinical study, 48 patients were evaluated for response. According to the study authors, the overall RR was 31% (95% CI, 26% to 57%), with a median PFS of 4.6 months (95% CI, 2.8 to 5.6 months). RR was 41% (95% CI, 26% to 57%) in KRAS WT tumors, with a median PFS of 5.6 months (95% CI, 2.9 to 5.6 months). There was no response in 11 patients with KRAS mutations. Frequent grade 3 and 4 toxicities were rash (48%), hypomagnesaemia (18%), and fatigue (10%).
The study authors concluded that due to its inhibitory effects on the growth of colon cancer cells in vitro, as well as its clinical efficacy in patients with KRAS WT, metastatic colorectal cancer, the combined therapy of cetuximab and erlotinib merits further evaluation in randomized clinical studies.