Quality of life in patients with K‐RAS wild‐type colorectal cancer

Abstract

BACKGROUND 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). METHODS 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. RESULTS 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. CONCLUSIONS 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. Cancer 2014;120:181–189. © 2013 American Cancer Society.

A multi-targeted approach to suppress tumor-promoting inflammation

“…Cancers harbor significant genetic heterogeneity [37], and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, a lack of success, rising drug costs and significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics [38]. Consequently, this approach aims to target many disease-specific pathways simultaneously - using low-cost chemistry with little to no toxicity - to address this heterogeneity (in contrast to the limited number of actionable targets that have become the norm in combination chemotherapy).…”

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“…Combining brivanib with cetuximab increased toxicity compared to cetuximab alone, with the overall incidence of Pgrade 3 AEs at 78% vs. 53% (p < .001), respectively [33]. HRQL analysis showed a shorter time to quality of life deterioration among patients treated with brivanib alaninate plus cetuximab compared to control, potentially due to increased rates of fatigue and gastrointestinal AEs [34].…”

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“…In fact, the combination of the two drugs led to an accelerated deterioration of HRQoL compared with single-agent cetuximab. The researchers suggested that this could be a result of the increased toxicity of the combined therapy, with the side effects offsetting any potential HRQoL benefit of delayed disease progression [32]. …”