Patients with the lowest body mass index (BMI) had the shortest overall survival in an analysis of bevacizumab studies in metastatic colorectal cancer (mCRC) presented for the first time at the ESMO 17th World Congress on Gastrointestinal Cancer 2015 in Barcelona.
"There is good evidence that obesity increases the risk of getting colorectal cancer and that it increases the risk of colorectal cancer recurrence after curative therapy," said lead study author Dr Yousuf Zafar, associate professor of medicine at Duke Cancer Institute in Durham, North Carolina. "What we did not know prior to these results is whether there is a relationship between obesity and survival in patients with metastatic colorectal cancer."
He continued: "There is evidence that, at least in the US, obese patients may be at risk to receive lower doses of chemotherapy, so we hypothesised that obesity would be associated with worse survival in patients with colorectal cancer."
The current study analysed overall survival and progression-free survival according to four categories of BMI (<25, 25-<30, 30-35, >35 kg/m2) in patients treated with bevacizumab in the first line for mCRC. The researchers used a pooled dataset of patients with previously untreated mCRC who received bevacizumab with chemotherapy in four large prospective US and European registry studies, namely BEAT, BRiTE, AWB and CONCERT.
"There is good evidence that obesity increases the risk of getting colorectal cancer and that it increases the risk of colorectal cancer recurrence after curative therapy," said lead study author Dr Yousuf Zafar, associate professor of medicine at Duke Cancer Institute in Durham, North Carolina. "What we did not know prior to these results is whether there is a relationship between obesity and survival in patients with metastatic colorectal cancer."
He continued: "There is evidence that, at least in the US, obese patients may be at risk to receive lower doses of chemotherapy, so we hypothesised that obesity would be associated with worse survival in patients with colorectal cancer."
The current study analysed overall survival and progression-free survival according to four categories of BMI (<25, 25-<30, 30-35, >35 kg/m2) in patients treated with bevacizumab in the first line for mCRC. The researchers used a pooled dataset of patients with previously untreated mCRC who received bevacizumab with chemotherapy in four large prospective US and European registry studies, namely BEAT, BRiTE, AWB and CONCERT.
A total of 6,128 patients were included in the analysis, which showed that patients with the lowest BMI (<25 kg/m2) had a significantly shorter overall survival than patients in the other BMI categories (see table). Progression-free survival was similar across all BMI subgroups.
Zafar said: "Our primary finding was that obesity was not associated with worse survival in mCRC. Contrary to our hypothesis, patients who had the lowest BMI were at risk of having the shortest survival. This effect persisted after adjusting for study, age, ECOG performance status, gender, and hypertension. We did not see any relationship between BMI and progression-free survival."
With regard to how the findings might be explained, Zafar said: "When it comes to obesity and colorectal cancer incidence and recurrence, there is likely some biologic mechanism that increases that risk, which may be related to factors including insulin or insulin-like growth factor. However, in the relationship between obesity and survival in metastatic colorectal cancer, it's likely that cancer-related cachexia overwhelmed any potential biologic harm from obesity or any potential inadequate dosing that obese patients may experience."
He added: "These results suggest that cachexia is a fairly strong predictor of poor outcomes in these patients. This could be a biologic effect or a treatment pattern issue. Cachexia by itself is a poor prognostic indicator but there also may be a relationship between cachexia and how much treatment patients can tolerate. I would hypothesise that the lowest weight patients in our analysis received or tolerated less treatment."
Patients with the lowest BMI had similar progression-free survival to those in the other BMI categories. Zafar explained: "It's possible that the lowest weight patients may receive adequate first-line treatment but then are too sick to receive subsequent lines of therapy. That may be where we can focus more attention on improving their outcomes."
Looking to the future of this research area, Zafar said: "An important next step in this work would be a closer study of how cachexia worsens patient outcomes in mCRC. We need to understand whether it is the biology of cachexia that harms these patients more, or whether their outcome is worsened by receipt of sub-par treatment. Or it could be a combination of both."
Commenting on the data, Dr Roberto Labianca, Director of the Cancer Centre, Ospedale Giovanni XXIII in Bergamo, Italy, ESMO spokesperson, said: "This study is important because we can now consider BMI as a prognostic factor for patients with metastatic colorectal cancer. The clinical implication could be that patients with low BMI should be considered similar to patients with more aggressive cancer and probably they should be given more active treatment. For example, polychemotherapy instead of monotherapy or a biological plus chemotherapy instead of chemotherapy alone."
"We need more follow up of course," continued Labianca. "The next step could be to design a prospective clinical trial using BMI to stratify patients for treatment."
ESMO 17th World Congress on Gastrointestinal Cancer 2015 in Barcelona
Zafar said: "Our primary finding was that obesity was not associated with worse survival in mCRC. Contrary to our hypothesis, patients who had the lowest BMI were at risk of having the shortest survival. This effect persisted after adjusting for study, age, ECOG performance status, gender, and hypertension. We did not see any relationship between BMI and progression-free survival."
With regard to how the findings might be explained, Zafar said: "When it comes to obesity and colorectal cancer incidence and recurrence, there is likely some biologic mechanism that increases that risk, which may be related to factors including insulin or insulin-like growth factor. However, in the relationship between obesity and survival in metastatic colorectal cancer, it's likely that cancer-related cachexia overwhelmed any potential biologic harm from obesity or any potential inadequate dosing that obese patients may experience."
He added: "These results suggest that cachexia is a fairly strong predictor of poor outcomes in these patients. This could be a biologic effect or a treatment pattern issue. Cachexia by itself is a poor prognostic indicator but there also may be a relationship between cachexia and how much treatment patients can tolerate. I would hypothesise that the lowest weight patients in our analysis received or tolerated less treatment."
Patients with the lowest BMI had similar progression-free survival to those in the other BMI categories. Zafar explained: "It's possible that the lowest weight patients may receive adequate first-line treatment but then are too sick to receive subsequent lines of therapy. That may be where we can focus more attention on improving their outcomes."
Looking to the future of this research area, Zafar said: "An important next step in this work would be a closer study of how cachexia worsens patient outcomes in mCRC. We need to understand whether it is the biology of cachexia that harms these patients more, or whether their outcome is worsened by receipt of sub-par treatment. Or it could be a combination of both."
Commenting on the data, Dr Roberto Labianca, Director of the Cancer Centre, Ospedale Giovanni XXIII in Bergamo, Italy, ESMO spokesperson, said: "This study is important because we can now consider BMI as a prognostic factor for patients with metastatic colorectal cancer. The clinical implication could be that patients with low BMI should be considered similar to patients with more aggressive cancer and probably they should be given more active treatment. For example, polychemotherapy instead of monotherapy or a biological plus chemotherapy instead of chemotherapy alone."
"We need more follow up of course," continued Labianca. "The next step could be to design a prospective clinical trial using BMI to stratify patients for treatment."
ESMO 17th World Congress on Gastrointestinal Cancer 2015 in Barcelona
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