Quality of Life in Patients With K-RAS Wild-Type Colorectal Cancer: The CO.20 Phase 3 Randomized Trial

• Published in: Cancer Vol. 120; no. 2; pp. 181 - 189
• Main Authors: RINGASH, Jolie, AU, Heather-Jane, ALCINDOR, Thierry, NG, Siobhan, SALIM, Muhammad, SABESAN, Sabe, EASAW, Jay C, SHANNON, Jenny, EL-TAHCHE, Fabyolla, WALTERS, Ian, DONGSHENG TU, O'CALLAGHAN, Christopher J, SIU, Lillian L, SHAPIRO, Jeremy D, JONKER, Derek J, ZALCBERG, John R, MOORE, Malcolm J, STRICKLAND, Andrew, KOTB, Rami, JEFFERY, Mark
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 15.01.2014
• Subjects: Alanine - administration & dosage; Alanine - analogs & derivatives; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cetuximab; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Diarrhea - chemically induced; Fatigue - chemically induced; Gastroenterology. Liver. Pancreas. Abdomen; Genes, ras; Humans; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Quality of Life; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surveys and Questionnaires; Time Factors; Treatment Outcome; Triazines - administration & dosage; Tumors; Phase III trial; Rectal disease; Prognosis; Questionnaire; Colorectal cancer; K ras Gene; Randomization; Cancerology; Intestinal disease; Evolution; Protooncogene; Human; patient-reported outcomes; palliative chemotherapy; Malignant tumor; Wild type; Quality of life; Colonic disease; questionnaires; Chemotherapy; Treatment; K-RAS; C-Onc gene; Digestive diseases; Onc gene; Cancer; colorectal cancer; quality of life
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28410

The CO.20 trial randomized patients with K-RAS wild-type, chemotherapy-refractory, metastatic colorectal cancer to receive cetuximab (CET) plus brivanib alaninate (BRIV) or CET plus placebo (CET/placebo). Quality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 at baseline and at 2, 4, 6, 8, 12, 16, and 24 weeks until disease progression. Predefined coprimary QoL endpoints were time to deterioration (first worsening from baseline of ≥ 10 points) on the Physical Function (PF) and Global (GHS) scales. Of 750 randomized patients, 721 (358 of whom received CET/BRIV) were assessable for QoL. QoL compliance and baseline PF and GHS scores did not differ by treatment arm. The median time to deterioration was 1.6 months versus 1.1 months for GHS (P =.02) and 5.6 months versus 1.7 months for PF (P <.0001) favoring CET/placebo. Secondary analysis favored CET/placebo for QOL response on the PF, Cognitive Function, Fatigue, Nausea, Appetite, and Diarrhea scales. A greater percentage of patients on the CET/BRIV arm had PF worsening at 6 weeks (31% vs 17%). Clinical adverse events of ≥ grade 3 were more common with CET/BRIV than with CET/placebo, including fatigue (25% vs 11%), hypertension, rash, diarrhea, abdominal pain, dehydration, and anorexia. Compared with CET/placebo, the combination of CET/BRIV worsened time to QoL deterioration for patients with K-RAS wild-type, chemotherapy-refractory, metastatic colorectal cancer on the PF and GHS scales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. This result may be due to higher rates of fatigue and gastrointestinal adverse events.