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Higher BMI linked to better metastatic RCC outcomes
BY NEIL OSTERWEIL
Frontline Medical News
T
alk about a paradox: high body mass index
is a known risk factor for renal cell carci-
noma, but previous studies have shown
that patients with high BMI who develop
localised RCC generally present with lower
grade disease and have better outcomes than
normal-weight patients.
Now, investigators confirm that overweight
or obese patients with metastatic renal cell
carcinoma (mRCC) also tend to have a better
prognosis than their leaner counterparts when
treated with targeted therapies.
“We externally validate that BMI impacts
the outcome of patients with metastatic kidney
cancer treated with targeted therapy in terms
of overall survival, progression-free survival,
and overall response rates,” said Dr Laurence
Albiges, a visiting scientist in the Kidney Can-
cer Centre at the Dana-Farber/Brigham and
Women’s Cancer Centre, Boston.
Although the mechanism for a protective ef-
fect of excess weight is not clear, there is some
evidence to suggest that fatty acid metabolism
in mRCC may play a role, she said at the 2015
Genitourinary Cancers Symposium.
In tissues samples from The Cancer
GenomeAtlas (TCGA, a joint repository of the
National Cancer Institute and National Hu-
man Genome Research Institute), expression
of FASN, a gene that encodes for fatty acid
synthase, was associated with overall survival
(OS), but in other samples FASN expression
was not an independent prognostic factor for
OS, she said.
Investigate and verify
To clarify the role of BMI in mRCC, Dr Al-
biges and colleagues looked at data from clini-
cal trials, specimens from the International
Metastatic Renal Cell Carcinoma Database
Consortium (IMDC), and biologic data from
the TCGA.
As the group reported at the 2014 ASCO
annual meeting (Abstract 4576), they first
looked at the effect of low BMI (< 25 kg/m
2
)
vs high BMI (
≥
25) in 1,975 patients with
mRCC in clinical trials, and found that af-
ter adjustment for IMDC prognosis groups,
higher BMI was associated with better OS
(median 25.6 months vs 17.1 months; hazard
ratio, 0.84; P = 0.0079) and longer time to
treatment failure (median 8.1 vs 5.7 months;
HR, 0.86; P = 0.0067).
They then, in collaboration with Pfizer
Oncology, conducted an external validation
study using data on 4,657 patients with mRCC
treated in phase II–III clinical trials from 2003
through 2013.
After adjustment for various risk factors,
they found again that BMI of 25 or greater
was associated with better outcomes in terms
of overall survival (23.4 vs 14.5 months; HR,
0.830; P = 0.0008), progression free survival
(8.2 vs 5.5 months; HR, 0.821; P < 0.0001),
and overall response rate (25.3% vs 17.6; ad-
justed odds ratio, 1.527; P < 0.0001).
Dr Albiges noted that when patients were
stratified by histologic subtype, “the favourable
outcome associated with high BMI was only
observed in clear cell RCC.”
The investigators next looked at informa-
tion from the TCGA dataset on patients with
metastatic clear cell RCC to see whether there
was correlation between BMI and survival and
between BMI and FASN expression. Although
they did not detect a significant survival
advantage for higher BMI in this cohort, they
did find that higher BMI was significantly as-
sociated with lower FASN expression levels
(P = 0.034), and that FASN expression below
the median level was associated with better
overall survival (P = 0.002).
Finally, they examined biospecimens from
the IMDC dataset with information about
outcomes under targeted therapy. Here, they
found that FASN staining was associated with
prognosis groups, but was not an independ-
ent prognostic factor for OS in multivariable
analysis.
“BMI, however, is associated with overall
survival independently of FASN,” Dr Albiges
said.
Although the mechanisms for the effect
of BMI on survival are not clear, the study
supports observations that many oncologists
have made in clinic, said Dr Ulka Vaisham-
payan, chair of genitourinary oncology at the
Karmanos Cancer Institute at Wayne State
University in Detroit.
“There is obviously, I think, a clinical gestalt
that we all have, that people who are not los-
ing a lot of weight are in general doing better
across a number of malignancies,” she said.
Dr Vaishampayan was the invited discussant.
Risk of lethal prostate cancer is lower for regular aspirin users
BY SUSAN LONDON
Frontline Medical News
R
egular aspirin use appears to protect against the develop-
ment of metastatic and fatal prostate cancer, according to
an analysis of the Physicians’ Health Study.
Investigators led by Dr Christopher Brian Allard analysed
data from 22,071 male physicians who were initially free of
prostate cancer and were prospectively followed from 1982
through 2009.
Results showed that after adjustment for age, race, body
mass index, and smoking status, men who took aspirin regu-
larly (more than three tablets a week) were 24% less likely to
develop lethal prostate cancer, which was defined in the study
as metastatic disease or death from prostate cancer, Dr Allard
reported in a press briefing held before the 2016 genitourinary
cancers symposium.
However, regular aspirin use did not reduce the risk of pros-
tate cancer overall, of high-grade prostate cancer, or of locally
advanced prostate cancer.
Further analyses restricted to the men who developed pros-
tate cancer showed that regular aspirin use after diagnosis was
associated with a 39% lower risk of dying from the disease. In
contrast, use before diagnosis did not have a protective effect.
“Our study demonstrates that regular aspirin intake may
inhibit lethal prostate cancer, probably by preventing cancer
progression,” said Dr Allard, a urologic oncology fellow at
Brigham and Women’s Hospital and Massachusetts General
Hospital, both in Boston. Also, “men with prostate cancer who
took aspirin regularly after diagnosis had a significantly reduced
risk of death.”
Although aspirin’s exact mechanism in preventing lethal
disease is unknown, preclinical data have implicated its anti-
platelet action, which is consistent with evidence suggesting
that circulating cancer cells may use platelets to escape im-
mune detection, he said. “That would explain why there is no
effect on the local cancer, but it is preventing deposition of
metastases into metastatic environments.”
The main shortcoming of the research was the lack of informa-
tion on aspirin dose, DrAllard acknowledged.Although the Physi-
cians’ Health Study began as a randomised trial in 1982 testing
325mg of the drug every other day, it was formally stopped 5 years
later after cardiovascular benefit was established, and participants
were free to take any dose thereafter. “We think most men started
at 325 [mg] but then 81 mg did become a popular dose, and we
really don’t know what they were taking,” he said.
“More work is needed to identify particular subsets of men
most likely to benefit from aspirin and to determine the optimal
aspirin dose,” Dr Allard said.
In terms of applying the findings to clinical care, he recom-
mended an individualised approach. “The main thing to keep
in mind is that although aspirin is over the counter, there are
side effects and potential harms. That being said, we don’t have
the results of a randomised clinical trial looking at aspirin for
prostate cancer survival yet,” he said. So men who are inter-
ested in aspirin for prevention of lethal prostate cancer should
talk to their physicians, he added, “and look at their personal
risks of side effects and harms from aspirin, as well as their
benefits in terms of both prostate cancer and also potential
cardiovascular benefits. It needs to be a personalised decision
for every individual patient.”
Dr Sumanta Pal, ASCO spokesperson and moderator of
the press briefing, agreed that the trial left unanswered some
critical questions and that clinicians must weigh the potential
harms of aspirin therapy against the observed benefits.
“While this work is provocative, it’s important to keep in mind
that the findings were from an observational study in which
surveys and a review of hospital records were used to obtain in-
formation,” added Dr Pal, a medical oncologist at City of Hope in
Duarte, California. “These studies are certainly thought provok-
ing but are perhaps best followed by formal clinical trials where
we compare use of aspirin either to no treatment or perhaps to
placebo.”
Dr Allard disclosed that he had no conflicts of interests. The Pros-
tate Cancer Foundation and the National Institutes of Health/
National Cancer Institute funded the trial. Dr Pal disclosed that
he receives honoraria from Astellas Pharma, Medivation, and
Novartis; that he has a consulting or advisory role with Aveo,
Genentech, Myriad Pharmaceuticals, Novartis, and Pfizer; and
that he receives research funding from Medivation.
There is obviously, a clinical gestalt
that we all have, that people who
are not losing a lot of weight are
in general doing better across a
number of malignancies.
© ASCO/Todd Buchanan 2016
Vol. 9 • No. 1 • 2016 •
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& O
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ASCO Genitourinary Cancers Symposium 2016