Early weight loss is an independent risk factor for shorter survival and increased side effects in patients with metastatic colorectal cancer undergoing first‐line treatment within the randomized Phase III trial FIRE‐3 (AIO KRK‐0306)

Abstract

Body weight loss is frequently regarded as negatively related to outcomes in patients with malignancies. This retrospective analysis of the FIRE‐3 study evaluated the evolution of body weight in patients with metastatic colorectal cancer (mCRC). FIRE‐3 evaluated first‐line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab or bevacizumab in mCRC patients with RAS‐WT tumors (ie, wild‐type in KRAS and NRAS exons 2‐4). The prognostic and predictive relevance of early weight loss (EWL) regarding patient outcomes and treatment side effects were evaluated. Retrospective data on body weight during first 6 months of treatment were evaluated (N = 326). To correlate with efficacy endpoints and treatment side effects, patients were grouped according to clinically significant EWL ≥5% and <5% at Month 3. Age constituted the only significant predictor of EWL following a linear relationship with the corresponding log odds ratio (P = .016). EWL was significantly associated with the incident frequencies of diarrhea, edema, fatigue, nausea and vomiting. Further, a multivariate analysis revealed EWL to be an independent negative prognostic factor for overall survival (32.4 vs 21.1 months; hazard ratio [HR]: 1.64; 95% confidence interval [CI] = 1.13‐2.38; P = .0098) and progression‐free survival (11.8 vs 9.0 months; HR: 1.72; 95% CI = 1.18‐2.5; P = .0048). In conclusion, EWL during systemic treatment against mCRC is significantly associated with patient age. Patients exhibiting EWL had worse survival and higher frequencies of adverse events. Early preventative measures targeted at weight maintenance should be evaluated, especially in elderly patients being at highest risk of EWL.

Association of Prediagnosis Obesity and Postdiagnosis Aspirin With Survival From Stage IV Colorectal Cancer

“…Specifically, patients with normal prediagnosis BMI were more likely to experience weight gain and had a lower likelihood of death compared with those with an overweight or obese prediagnosis BMI. Two recent clinical trial analyses found weight loss in late-stage CRC patients early in treatment or within 6 months prior to study enrollment independently projected poor outcomes, supporting the notion of weight loss as a potential indicator of disease progression and/or treatment toxicity. In contrast, several meta-analyses found a survival benefit among patients with postdiagnosis overweight BMI .…”

Body mass index, weight change, and cancer prognosis: a meta-analysis and systematic review of 73 cohort studies

“… 24 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 For weight change-related data, both HR data for OS and mortality data with events and total number of people in the exposed and non-exposed groups as initial data were retained ( n = 27). 24 , 26 , 41 , 48 , 51 , 76 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ,…”

“…Among these, two studies were included in the analysis of weight gain versus nonweight change, 24 , 41 with a total I 2 of 89% and an HR of 3.53 (95% CI 0.46-27.13; P = 0.23). Twenty studies were included in the analysis of weight loss versus nonweight loss, 24 , 26 , 41 , 48 , 51 , 76 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 98 , 99 , 104 , 105 , 106 with a total I 2 of 88% and an HR of 1.66 (95% CI 1.33-2.07; P < 0.0001), and the results were statistically significant. With different weight change threshold groupings, analyses of weight loss >10% versus weight loss <10% had an I 2 of 75% and an HR of 2.10 (95% CI 1.37-3.21; P = 0.0006), and the results were statistically significant.…”

Nutrition care is an integral part of patient-centred medical care: a European consensus

“…As such, despite a large body of individual studies demonstrating the value of early nutrition care in cancer, the overall body of evidence appears to remain inconclusive due to the relatively low number of studies which can be included at the level of a systematic review or meta-analysis. However, despite a relative lack of investment and a disproportionate focus on the legitimate difficulty in reversing refractory cachexia [68], perhaps the most important point to note is that there is consistent, robust evidence demonstrating the ability of a variety of early nutrition interventions to significantly improve clinical outcomes [28,60,[69][70][71]. Clinicians, patients, and stakeholders at every level need to understand that evidence-based patient-centred care includes nutrition and as such, its omission is a disservice to people living with and beyond cancer.…”