Yousuf Zafar, MD
Low body mass index (BMI) was associated with a worse median overall survival (OS) with first-line bevacizumab and chemotherapy in patients with metastatic colorectal cancer (mCRC), suggesting that BMI could serve as a potential prognostic factor for outcomes, according to a pooled dataset of more than 6000 patients presented at the 2015 World Congress on GI Cancer. Progression-free survival (PFS) was similar across all BMI subgroups in the analysis.
“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," said lead investigator Yousuf Zafar, MD, gastrointestinal oncologist & health services researcher, Oncology Department, Duke University Medical Center. "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.”
The full size of the dataset analyzed in the study was 6128 patients. The patients analyzed in the trial were participants in one of the prospective BEAT (ex-USA), BRiTE (USA), AWB (Germany), or CONCERT (France) studies. A fifth trial, ARIES, was identified but the data were not used in this analysis, since patient BMI had not been determined. The primary endpoint of the analysis was OS and PFS, as evaluated using the Kaplan-Meier method. BMI was used as a continuous variable and was stratified by baseline BMI categories, age, ECOG performance status, sex, and by each study in the dataset.
The median BMI for all patients was 25.3 kg/m2
(interquartile range [IQR], 22.6-28.7). BMI was divided into 5 categories of <20 (n = 532), 20 to 24 (n = 2328), 25 to 29 (n = 2119), 30 to 35 (n = 821), and ≥35 kg/m2
(328). The majority of patients (n = 5554) had an ECOG PS of 0 or 1 and the site of the primary tumor was the colon, rectum, rectum and colon, and recto-sigmoid. Nearly all patients (86%) had undergone surgical resection.
Although PFS was similar across baseline BMI categories, a difference in OS was observed. Patients with BMIs <25, 25 to 29, 30 to 35, and ≥35 kg/m2
demonstrated a median PFS of 10.0, 10.6, 10.5 and 10.9 months, respectively. The median OS in the same respective categories was 21.1 (95% CI, 20.2-22.0), 23.5 (95% CI, 22.5-24.7), 24.0 (95% CI, 22.0-25.8), and 23.7 (95% CI, 21.6-25.2) months.
“Proportional hazards models confirmed that low BMI was associated with shortened OS after adjusting for potential differences in baseline characteristics,” commented Zafar.
According to a proportional hazard model using BMI as a continuous variable, a BMI increase of 5 kg/m2
was associated with a decrease in the risk of death (hazard ratio [HR] = 0.911; 95% CI, 0.879-0.944).
For those with a BMI <20 versus <25, the HR was 1.18. For <20 in comparison with >25, the HR was 1.32. In those with a BMI of >25 kg/m2
, the HR compared with <20 was 1.12. Using BMI as a categorical variable and adjusting for hypertension at baseline showed a similar pattern across the respective categories.
“I see this study as hypothesis generating and a basis for a randomized, controlled study,” said Zafar, during a question and answer session.
The role of high BMI has only recently been evaluated in mCRC, revealing obesity as a risk factor for developing colon cancer. Also, patients with BMI at both the lowest (<18.5 kg/m2
) and highest (≥35 kg/m2
) levels have been shown to be at higher risk for earlier disease recurrence following adjuvant chemotherapy for colon cancer.
“Although high BMI has been associated with increased risk of colorectal cancer, little is known about how BMI impacts outcomes for patients already diagnosed with mCRC,” remarked Zafar. “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.”
Zafar Y, Hubbard J, Van Cutsem E, et al. Survival outcomes according to body mass index (BMI): results from a pooled analysis of 5 observational or phase IV studies of bevacizumab in metastatic colorectal cancer (mCRC). Presented at: 17th World Congress on Gastrointestinal Cancer; July 1-4, 2015; Barcelona, Spain. Abstract LBA-01.
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