Haematology+Oncology_News

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BCG/sunitinib combo produces high
complete response rate in NMIBC
BY NEIL OSTERWEIL
Frontline Medical News
Acombination of intravesical bacillus Calmette-
Guerin (BCG) followed by sunitinib produced
high complete response rates in patients with
high-risk, non-muscle invasive bladder cancer.
In a phase II trial, 26 of 36 patients (72%) with
non-muscle invasive bladder cancer (NMIBC)
had a complete response following bladder
installation of BCG and consolidation therapy
with sunitinib (Sutent), reported Dr Alexander
M. Helfand of the University of Michigan Com-
prehensive Cancer Centre, Ann Arbor.
“Adding sunitinib after BCG induction may
result in increased rates of complete response at
3 months over those of BCG alone. The durability
of response appears promising, given a 77% 2-year
recurrence in high-risk patients with non-muscle
invasive bladder cancer,” he said at the 2015
Genitourinary Cancers Symposium sponsored
by the American Society of Clinical Oncology.
“Certainly, this study provides the rationale
to consider antiangiogenic therapy in the non-
muscle invasive setting,” said Dr Jonathan E.
Rosenberg of Memorial Sloan Kettering Cancer
Centre, New York, the invited discussant.
Induction and maintenance therapy with BCG
is the mainstay of initial treatment of high-risk
NMIBC. It has been associated in clinical studies
with 3-month complete response rates ranging
from 28% to 85%, 5-year cumulative recurrence
rates from 50% to 55%, 5-year cumulative progres-
sion rates of 8–20%, and a 10-year disease-specific
mortality rate of 4–25%, Dr Helfand noted.
“Complete response to BCG at 3 months has
been shown to predict future recurrence-free sta-
tus. Consolidating the initial tumour response to
BCG with adjunctive therapies may help improve
outcomes,” he said.
BCG downregulates vascular endothelial
growth factor (VEGF) receptors, and sunitinib
binds to VEGF receptors to prevent vascular
growth.
To see whether the combined therapies could
act synergistically, investigators treated patients
with 6-weeks of BCG induction beginning within
6 weeks of diagnostic or restaging biopsy, followed
by a 2-week hiatus, then 28 days of oral sunitinib
50 mg/day. Patients with a complete response at 3
months went on to BCGmaintenance, while those
with an incomplete response or recurrence at 3
months went on to a second cycle of BCG followed
by sunitinib. Patients with disease progression after
either treatment cycle were treated with alternative
therapies at the treating clinician’s discretion.
A total of 36 of 39 patients completed BCG
induction and at least one dose of sunitinib, and
these patients were included in the efficacy analy-
sis. The safety analysis was by intention to treat,
and therefore included all 39 patients.
The complete response rate at 3 months after
cycle one, the primary endpoint, was 73% (26 of
36 patients). Of the responders, 73% have started
on BCG maintenance, 23% had no maintenance
BCG and no evidence of disease at last follow-up,
and the remaining 4% had cystectomies.
Of the 28% (10 patients) with residual disease
at 3 months, four underwent cystectomy, two had
Ta low-grade recurrences which were managed
with repeat resection, and two elected a second
BCG induction/sunitinib cycle.
There were a total of 127 adverse events
deemed to be minor among 34 patients, and 6
major adverse events occurring in 5 patients.
The major events included rash on hands and
feet, hand and foot syndrome, thrombocytopenia,
febrile diarrhoea, sores on hands and feet, and
reactivation of herpes zoster.
In all, 13 patients required some delay of suni-
tinib therapy, primarily due to jaundice/elevated
liver enzymes or thrombocytopenia. All adverse
events disappeared at the end of therapy.
Of the 31 patients with an intact bladder, 2
years recurrence-free survival was 77%, and 2-year
progression-free survival was 100%.
Dr Rosenberg, the discussant, noted that over-
all “the results look quite good. Toxicity and toler-
ability, though, do make me concerned, and future
trials might consider dose reduction [of sunitinib]
at the start to 37.5 mg to actually increase the
number of patients and time on therapy.”
Dasatinib adds no survival benefit to docetaxel in mCRPC
BY NASEEM S. MILLER
Frontline Medical News
Adding dasatinib to standard-of-care chem-
otherapy led to a modest delay in skeletal-
related events but did not improve overall
survival for patients with metastatic castrate-
resistant prostate cancer in the READY trial.
Dasatinib, a tyrosine kinase inhibitor,
showed promising results in phase I and II
studies, but fell short in READY, a multina-
tional randomised double-blinded, placebo-
controlled study, sponsored by Bristol-Myers
Squibb.
With no difference in overall survival and no
meaningful changes in the study’s secondary
endpoints, the search continues for treat-
ments for this group of patients whose cur-
rent options are mostly palliative with modest
improvements in survival. The observed delay
in skeletal-related events with dasatinib is be-
ing further investigated, said the study’s lead
author, Dr John C. Araujo of the University of
Texas MDAnderson Cancer Centre, Houston.
In READY, 1522 patients were randomised
to receive docetaxel (75 mg/m2, three times
a week) plus prednisone and either 100 mg
daily of dasatinib (762 patients), or placebo
(760 patients).
There were no meaningful differences in
the demographics or disease characteristics
of the two study arms. Patients were treated
until disease progression or they had unac-
ceptable toxicity.
The primary endpoint of the study was
overall survival. The secondary endpoints were
objective response rates, time to first skeletal-
related event, time to prostate-specific antigen
progression, urinary N-telopeptide (uNTx)
reduction, pain reduction, progression-free
survival, and safety.
Overall survival was 21.5 months in the
dasatinib group and 21.2 months in the
placebo group (hazard ratio, 0.99; P = 0.90).
Comparably similar outcomes were seen in
secondary endpoints for dasatinib vs placebo
arm: objective response rates were 30.5% and
31.9%, respectively; median time to prostate-
specific antigen progression was 8 months
vs 7.6 months; uNTx reduction was 66% vs
60.6%; pain reduction was 66.6% vs 71.5%;
progression-free survival was 11.8 months vs
11.1 months.
The one exception was median time to first
skeletal event, which was not reached in the
dasatinib group and was in 31.1 months for
the placebo group.
Dr William Oh, chief of haematology and
medical oncology at Tisch Cancer Institute
and the Mount Sinai School of Medicine,
New York, commented that “about two-thirds
of the patients were not on bisphosphonates,
which may explain why there was a trend
toward a benefit in terms of (skeletal-related
events)” in the dasatinib arm.
DrAraujo reported there were no unexpected
safety findings and no unanticipated events.
Patients came off the trial for similar reasons
in both arms, including disease progression and
maximum clinical benefit. Adverse events re-
lated to treatment included diarrhoea, fatigue,
alopecia, and nausea and occurred in 18% of
patients in the dasatinib arm and in 9% in the
placebo arm. Grade 3–4 adverse events of inter-
est included anaemia (8% vs 5.9% in placebo),
neutropenia (6.2% vs 5.5%), hypocalcaemia
(3.5% vs 3.1%), gastrointestinal bleeding (2.6%
vs 1.3%), and pleural effusion (1.3 vs 0.4%).
Dr Araujo has received research funding from
Bristol-Myers Squibb, the maker of Sprycel and
sponsor of the trial. Dr Oh has been consultant
or adviser for Amgen, Astellas Pharma, Bayer,
Bellicum Pharmaceuticals, Dendreon, Janssen
Biotech, Medivation, and Pfizer. He has received
research funding from Millennium.
ASCO Genitourinary
Cancers
Symposium 2016
7–9 January 2016 •
San Francisco, California
The 2016 Genitourinary Cancers
Symposium was a 3-day scientific
and education meeting sponsored
by the American Society of
Clinical Oncology. On pages 6
and 7, we bring you selected
reports from our coverage of the
meeting, including on aspirin’s
potential protective effect against
fatal prostate cancer, BMI and
its impact on the outcome of
patients with metastatic kidney
cancer, and trials that failed
to boost survival of men with
metastatic castration-resistant
prostate cancer.
The results look quite good. Toxicity
and tolerability, though, do make me
concerned.
Dr Fred Saad, professor and
chief of urology and director of
G-U Oncology at the University of
Montreal Hospital Centres, deliv-
ers highlights of the past year’s
prostate cancer research at the
ASCO GU symposium. He point-
ed out that “although there were
no new drugs approved in 2015,
we learned a lot about what we
have available – some good and
some not so good.”
From a clinical perspective, and
with a focus on topics that con-
firm or change current practice,
PracticeUpdate summarises
five key topics from prostate
cancer research published in
2015: screening and active sur-
veillance (Part 1); local therapy
(Part 2); and androgen deprivation
therapy, chemotherapy in men
with hormone-sensitive disease,
and new options in metastatic
prostate cancer (all in Part 3).
This exclusive report is available
on
PracticeUpdate is an Elsevier website.
© ASCO/Todd Buchanan 2016
Haematology & O ncology News • Vol. 9 • No. 1 • 2016
NEWS
6
CONFERENCE COVERAGE