Cancer prevention
field riding high into the
new year
2
ACOG recommends against
annual cervical cancer
screening
4
ASCO Genitourinary Cancers
Symposium 2016
BCG/sunitinib combo
produces high complete
response rate in NMIBC
6
Higher BMI linked to better
metastatic RCC outcomes
7
San Antonio Breast Cancer
Symposium 2015
BRCA mutation predicts
neoadjuvant therapy
benefit but is not strongly
prognostic
8
Neratinib shows consistent
breast cancer benefit
at 3 years
10
Pembrolizumab shows
promise in PD-L1–positive
breast cancer
11
American Society of
Haematology 2015
Heavily pretreated
myeloma responds to
pembrolizumab combo
12
First shot across the
bow for CAR T cells in
multiple myeloma
13
Genes tag increased
risk for avascular necrosis
in ALL patients under
age 10
14
2015 practice changers in
oncology: FDA-approved
EGFR TKIs for acquired
resistance to targeted
therapy in lung cancer
15
IN THIS ISSUE
Taxanes retain efficacy
against mCRPC resistant
to AR-antagonists
BY NEIL OSTERWEIL
Frontline Medical News
At the Genitourinary Cancers Symposium, San Francisco
T
he variant, labelledAR-47, is a truncated form of
the androgen receptor that is missing the ligand-
binding domain, to which both androgens and
androgen receptor inhibitors such as abiraterone
and enzalutamide normally bind. AR-V7 has been
detected in about one-third of men with metastatic
castration-resistant prostate cancer (mCRPC).
But a study of circulating tumour cells (CTCs)
from 37 men with mCRPC shows that patients
whose tumour cells are positive for AR-V7 retain
their sensitivity to taxanes.
“In this particular study, there was a 41% re-
sponse rate to taxanes if a man was AR-V7-positive,
compared to a 0% response to abiraterone or en-
zalutamide in this setting,” said Dr Emmanuel S.
Antonarakis from the Johns Hopkins Sidney Kimmel
Comprehensive Cancer Centre, Baltimore. Dr An-
tonarakis presented the study in a briefing prior to its
presentation in a poster session at the Genitourinary
Cancers Symposium sponsored by the American
Society of Clinical Oncology.
Testing for the presence of AR-V7 could in the
future help guide clinicians when choosing thera-
pies for men with mCRPC, Dr Antonarakis said.
The investigators used a quantitative
reverse-transcriptase polymerase
chain reaction (qRT-PCR) assay
to detect and quantify levels of AR-V7 in the CTCs
of 37 men with mCRPC who were scheduled to
start taxane-based chemotherapy with docetaxel
or cabazitaxel.
For the primary endpoint of a prostate specific
antigen (PSA) response, they found that 7 of 17
men (41%) who were positive for AR-V7 had a
response to taxane therapy, compared with 13 of
20 (65%) men with the wild type of the androgen
receptor (that is, AR-V7 negative). The difference in
response rates between AR-V7-positive and -nega-
tive men was not significant.
When they included data from an earlier study of
62 men treated with abiraterone or enzalutamide,
the investigators found that AR-V7-positive men
had significantly better progression-free survival
when treated with taxanes, compared with androgen
receptor antagonists. The hazard ratio (HR) for PFS
with taxanes was 0.21 (P = 0.003). In contrast, PFS
was similar for AR-V7-negative men treated with
either taxanes or abiraterone/enzalutamide.
“AR-V7 may potentially serve as a treatment se-
lection marker for men with metastatic castration-
resistant prostate cancer seeking therapy with either
taxanes or enzalutamide/abiraterone. However, be-
fore the data become clinically actionable, we need
to prospectively validate this finding in at least one
multicentre clinical trial,” Dr Antonarakis said. He
noted that there is currently no commercial assay
for AR-V7.
AR-V7 may potentially
serve as a treatment
selection marker for men
with metastatic castration-
resistant prostate cancer
seeking therapy with either
taxanes or enzalutamide/
abiraterone.
Nonalcoholic fatty liver disease linked to liver cancer without cirrhosis
BY AMY KARON
Frontline Medical News
From Clinical Gastroenterology
and Hepatology
A
bout 13% of US veterans with
hepatocellular carcinoma had no
evidence of preexisting cirrhosis,
according to a report published in the
January issue of
Clinical Gastroenter-
ology and Hepatology.
“The main risk factors for this entity
were nonalcoholic fatty liver disease
[NAFLD] or metabolic syndrome” –
not hepatitis C virus infection [HCV],
HBV [hepatitis B virus] infection, or al-
cohol abuse, said Dr Sahil Mittal of the
Michael E. DeBakey Veterans Affairs
Medical Centre and Baylor College of
Medicine in Houston. Screening all
patients with NAFLD for hepatocel-
lular carcinoma [HCC] is impractical,
so studies should seek “actionable risk
factors” or biomarkers that reliably
identify NAFLD patients who are at
particular risk of HCC, wrote Dr Mit-
tal and his coinvestigators.
Researchers have debated whether
chronic HCV infection or alcohol
abuse can lead to HCC in the absence
of cirrhosis, while at least one study has
shown that NAFLD can predispose
patients to this disease entity (
Arch
Pathol Lab Med
2008;132:1761–6).
But few studies have systematically
examined risk factors for HCC with-
out cirrhosis in the general population,
the investigators said. Therefore, they
randomly selected 1500 patients from
the US. Veterans Affairs system who
were diagnosed with HCC between
2005 and 2010 on the basis of histo-
pathology or established imaging cri-
teria (
Hepatology
2005;42:1208–36).
They reviewed complete medical
records for these patients, and classi-
fied those who did not have cirrhosis
according to the quality of supporting
histology, laboratory, and imaging data
(
Clin Gastroenterol Hepatol
2015. doi:
0.1016/j.cgh.2015.07.019).
In all, 3% of the cohort had level
1 (“highest-quality”) evidence for not
having cirrhosis, while another 10%
had level 2 evidence for no cirrhosis,
the investigators said. “Compared
with HCC in the presence of cirrho-
sis, these patients were more likely to
have metabolic syndrome or NAFLD
or no identifiable risk factor, and less
likely to have alcohol abuse or HCV
infection,” they added. Only two-
thirds of NAFLD patients with HCC
had cirrhosis, compared
with 91% of patients with
chronic HCV infection,
92% of HCV-infected pa-
tients, and 88% of patients
with an alcohol use disorder.
Notably, the odds of HCC
in the absence of cirrhosis
were more than five times
higher when patients had
NAFLD (odds ratio [OR],
5.4; 95% confidence interval
[CI], 3.4–8.5) or metabolic
syndrome (OR, 5.0; 95% CI, 3.1–7.8)
compared with HCV infection.
Patients with cirrhosis often go
unscreened for HCC even though
they are at greatest risk of this can-
cer. Therefore, trying to screen all
patients with NAFLD for HCC would
be “logistically impractical,” particu-
larly when the absolute risk of HCC
in noncirrhotic patients is unknown
and no one has examined the best
ways to screen this population, the
investigators said. Instead, clinicians
could prioritise screening and treating
NAFLD patients for diabetes mellitus
and obesity, both of which are associ-
ated with HCC. “There is evidence to
suggest that metformin reduces the
risk of HCC among diabetics,” they
added. “Studies of these and other
risk factors of HCC among NAFLD
patients with and without cirrhosis are
needed.”
Most patients in the study were
male, potentially limiting the general-
isability of the findings, the research-
ers noted.
The American National Cancer In-
stitute, the Houston Veterans Affairs
Health Services Research and Develop-
ment Centre of Excellence, the Michael
E. DeBakey Veterans Affairs Medical
Centre, and the Dan Duncan Cancer
Centre funded the study. The research-
ers had no disclosures.
By Nephron via Wikimedia Commons, Creative Commons license.
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Vol. 9 • No. 1 • 2016