ABSTRACT
The 20th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, 28-29 September 2018. This interactive multidisciplinary conference is attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancers. In addition, invited speakers from other provinces participate. Surgical, medical, and radiation oncologists, and allied health care professionals participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancers.
Subject(s)
Gastrointestinal Neoplasms , Practice Guidelines as Topic , Biomarkers, Tumor , Consensus , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/radiotherapy , Gastrointestinal Neoplasms/surgery , Gastrointestinal Neoplasms/therapy , Humans , Hyperthermia, Induced , Neoadjuvant TherapyABSTRACT
BACKGROUND: Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit. METHODS: Tumour samples from a phase III clinical trial of cetuximab plus best supportive care (BSC) vs BSC alone (CO.17) were analysed for EREG mRNA gene expression. Predictive effects of high vs low EREG on OS and progression-free survival (PFS) were examined for treatment-biomarker interaction. RESULTS: Both EREG and K-ras status were ascertained in 385 (193 cetuximab, 192 BSC) tumour samples. Within the high EREG and K-ras wild-type status ('co-biomarker')-positive group (n=139, 36%), median PFS was 5.4 vs 1.9 months (hazard ratio (HR) 0.31; P<0.0001), and median OS was 9.8 vs 5.1 months (HR 0.43; P<0.001) for cetuximab vs BSC, respectively. In the rest (n=246, 64%), PFS (HR 0.82; P=0.12) and OS (HR 0.90; P=0.45) were not significantly different. Test for treatment interaction showed a larger cetuximab effect on OS (HR 0.52; P=0.007) and PFS (HR 0.49; P=0.001) in the co-biomarker-positive group. CONCLUSION: In pre-treated K-ras wild-type status colorectal cancer, patients with high EREG gene expression appear to benefit more from cetuximab therapy compared with low expression. Epiregulin as a selective biomarker requires further evaluation.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Colorectal Neoplasms/drug therapy , Epidermal Growth Factor/biosynthesis , ras Proteins/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Cetuximab , Clinical Trials, Phase III as Topic , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Disease-Free Survival , Epidermal Growth Factor/genetics , Epiregulin , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Mutation , Neoplasm StagingABSTRACT
BACKGROUND: Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signalling with activity against all three VEGF receptors. Bevacizumab is an anti-VEGF-A monoclonal antibody with clinical benefit in previously treated metastatic colorectal cancer (mCRC). METHODS: Patients with mCRC who had progressed following first-line therapy were randomised 1:1:1 to modified (m)FOLFOX6 plus cediranib (20 or 30 mg day(-1)) or bevacizumab (10 mg kg(-1) every 2 weeks). The primary objective was to compare progression-free survival (PFS) between treatment arms. RESULTS: A total of 210 patients were included in the intent-to-treat (ITT) analysis (cediranib 20 mg, n=71; cediranib 30 mg, n=73; bevacizumab, n=66). Median PFS in the cediranib 20 mg, cediranib 30 mg and bevacizumab groups was 5.8, 7.2 and 7.8 months, respectively. There were no statistically significant differences between treatment arms for PFS (cediranib 20 mg vs bevacizumab: HR=1.28 (95% CI, 0.85-1.95; P=0.29); cediranib 30 mg vs bevacizumab: HR=1.17 (95% CI, 0.77-1.76; P=0.79)) or overall survival (OS). Grade ≥ 3 adverse events were more common with cediranib 30 mg (91.8%) vs cediranib 20 mg (81.4%) or bevacizumab (84.8%). CONCLUSION: There were no statistically significant differences between treatment arms for PFS or OS. When combined with mFOLFOX6, the 20 mg day(-1) dose of cediranib was better tolerated than the 30 mg day(-1) dose.
