The FDA has now approved four additional
checkpoint inhibitors for bladder cancer:
Bavencio (avelumab), Imfinzi (durvalumab),
Keytruda (pembrolizumab) and Opdivo (nivolumab).
Surgery and chemotherapy are still considered
the standard of care for bladder cancer. However,
patients on chemotherapy whose cancer progresses
or who, like Pritchard, are unable to receive chemotherapy for other reasons now have viable treatment alternatives.
RESEARCH ON THE RISE
The number of clinical trials in bladder cancer has
grown since the time of Pritchard’s diagnosis in 2014.
For example, a recent search using Clinical Trials.gov,
an online repository of research trials, shows more
than 260 studies are enrolling patients with
Researchers are exploring the use of combinations
of immunotherapies or immunotherapy plus chemotherapy. For instance, a team led by researchers at
the Icahn School of Medicine at Mount Sinai in New
York City recently reported the results of a phase II
clinical trial showing that metastatic bladder
cancer patients, especially those whose tumors
carry DNA repair defects, may benefit from receiving
the chemotherapy drugs gemcitabine and cisplatin
together with Yervoy. A phase II trial set to begin
in September 2018 is analyzing this chemotherapy
combination plus Opdivo in patients with muscle-invasive bladder cancer.
There is also interest in combining existing checkpoint inhibitors with IDO inhibitors, which target
other proteins shown to help cancer escape the
immune system. (Of note, however, a phase III clinical
trial testing this combination approach in melanoma
recently ended in failure.) In March 2018, the FDA
granted breakthrough therapy designation to a drug
called enfortumab vedotin, which means the agency
is expediting its development and review, for use in
patients with locally advanced or metastatic bladder
cancer who have previously received checkpoint inhibitors. The treatment, while not an immunotherapy, targets a protein called nectin- 4 that’s highly expressed in
most metastatic bladder cancers. One study found that
about 50 percent of patients with metastatic urothelial
carcinoma responded to the treatment.
Researchers are also looking into combining
chemotherapy with drugs targeting a blood vessel
growth factor called VEGF. In addition, a phase II
clinical trial recently showed that about 40 percent
of patients whose metastatic urothelial cancers carry
mutations in the FGFR3 gene respond to treatment
with an oral drug called erdafitinib, which also
received the FDA’s breakthrough therapy designation for metastatic bladder cancer in March 2018.
The drug targets all FGFR proteins, including the
mutated FGFR3 found in as much as 20 percent of
metastatic bladder cancers. Researchers are also
exploring whether epigenetic drugs, some of which
can chemically alter the surface of DNA to influence
gene expression, might reinvigorate a response to
immunotherapy after it stops working.
“As a urologist who has been involved in clini-
cal trial research for the last 20 years, it’s been very
There is no standard or widely accepted screening test for bladder cancer, says
Stephanie Chisolm, director of education and research for the Bladder Cancer
Advocacy Network, based in Bethesda, Maryland. This can be a problem, because
the warning signs—including increased urgency to urinate and blood in the
urine—can be ambiguous. As a result, some bladder cancers aren’t caught until
after they’ve begun to invade muscle in the bladder wall, making them more
difficult to treat.
However, scientists are working to develop noninvasive urine tests that might
detect early bladder cancer and perhaps help to distinguish slow-growing cancers
from more aggressive ones, says David McConkey, a research scientist and
director of the Johns Hopkins Greenberg Bladder Cancer Institute in Baltimore.
As an example, an international team led by George Netto recently reported on a
urine test called UroSeek, which searches for the presence of 11 gene mutations
and gene duplications frequently found in bladder cancer. The study analyzed
570 patients considered at risk for bladder cancer and found that the UroSeek
test was positive in 83 percent of people who ended up developing cancer after
a median follow-up of 18 months. Such a test might also be useful in monitoring
patients who have already been treated for bladder cancer for signs of a
recurrence. Several other urine tests to monitor or detect bladder cancer are
also available or in development. —K.K.M.
DETECTING BLADDER CANCER