Quality of life (QoL) assessment in patients (pts) with K-RAS wild-type (WT) chemotherapy refractory metastatic colorectal cancer (mCRC) treated with cetuximab (CET) plus brivanib alaninate (BRIV) or placebo: Results of the NCIC Clinical Trials Group and AGITG CO.20 trial

• Published in: Journal of clinical oncology Vol. 30; no. 4_suppl; p. 542
• Main Authors: Ringash, Jolie, Au, Heather-Jane, Siu, Lillian L., Shapiro, Jeremy D., Jonker, Derek J., Zalcberg, John Raymond, Moore, Malcolm J., Strickland, Andrew H., Kotb, Rami, Jeffery, Mark, Alcindor, Thierry, Ng, Siobhan, Salim, Muhammad, Sabesan, Sabe S., Easaw, Jacob C., Shannon, Jennifer Anne, El-Tahche, Fabyolla, Walters, Ian B., Tu, Dongsheng, O'Callaghan, Christopher J.
• Format: Journal Article
• Language: English
• Published: 01.02.2012
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2012.30.4_suppl.542

Abstract only 542 Background: The CO.20 trial randomized pts with K-RAS WT chemotherapy refractory mCRC to receive CET + BRIV (Arm A) or CET + placebo (Arm B). Although overall survival (primary endpoint) was not significantly improved (HR=0.88, p=0.12) in this heavily pre-treated population, progression free survival (PFS) favoured Arm A (HR=0.72 p<0.0001). Methods: Patients with K-RAS WT mCRC previously treated with or with contraindications to a fluoropyrimidine, irinotecan, and oxaliplatin were randomized to a loading dose of IV CET followed by weekly IV CET + BRIV 800 mg PO daily or CET + placebo daily. QoL, a secondary endpoint, was assessed using the EORTC QLQ-C30 at baseline and at 2, 4, 6, 8, 12, 16 and 24 weeks until progression or clinical deterioration. Co-primary QoL endpoints were defined a priori as definitive deterioration (first worsening from baseline of ≥10 points) on the physical function (PF) and Global scales. Time to QoL deterioration (DET) was measured from randomization using the Hochberg procedure to adjust for multiple testing. Results: 721 (358 Arm A) of 750 randomized pts were assessable for QoL. QoL compliance did not differ by arm and declined in follow-up from 87% to 47% over time. Baseline Global and PF scores did not differ by arm. Median time to QoL DET was 1.6 vs 1.1 mo for Global (p=0.02) and 5.6 vs 1.7 mo. for PF (p<0.0001) in Arm B vs A, respectively. Secondary QoL response evaluation showed a greater proportion of patients on Arm A to have worsening on the PF (31 vs 17% at 6 wks) and cognitive functioning scales, and on the fatigue, nausea, appetite and diarrhea symptom scales. Clinical adverse events ≥ Grade 3 were more common on Arm A than B including fatigue (25 vs 10%), hypertension, rash, diarrhea, abdominal pain, dehydration and anorexia. Conclusions: Despite a PFS benefit, the combination of CET + BRIV worsened time to QoL DET on the PF and Global scales of EORTC QLQ-C30 in pts with chemotherapy refractory K-RAS WT mCRC. This result may be due to higher rates of fatigue and gastrointestinal adverse events observed with the combination.